Report and Recommendations

Research on the Fetus

The National Commission for the Protection of

Human Subjects of Biomedical and

Behavioral Research

U.S. Department of Health, Education, and Welfare DHEW Publication No. (OS) 76-127

1975

National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research

Westwood Building, Room 125 5333 Westbard Avenue

Bethesda, Maryland 20016

July 25, 1975

Honorable Caspar W. Weinberger Secretary of Health, Education, and Welfare Washington, D.C. 20201

Dear Mr. Secretary:

On behalf of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, and pursuant to Section 202(b) of the National Research Act (Public Law 93-348), I am pleased to submit to you the Commission's Report and Recommendations: Research on the Fetus. An appendix volume, containing materials reviewed by the Commission in its deliberations, accompanies the report.

NATIONAL COMMISSION FOR THE PROTECTION OF HUMAN SUBJECTS OF BIOMEDICAL AND BEHAVIORAL RESEARCH

COMMISSIONERS

Kenneth John Ryan, M.D., Chairman Chief of Staff

Boston Hospital for Women

Joseph V. Brady, Ph.D. Professor of Behavioral Biology Johns Hopkins University

Robert E. Cooke, M.D. Vice Chancellor for Health Sciences University of Wisconsin

Dorothy I. Height President National Council of Negro Women, Inc.

Albert R. Jonsen, Ph.D. Adjunct Associate Professor of Bioethics University of California at San Francisco

Patricia King, J.D. Associate Professor of Law Georgetown University Law Center

Karen Lebacqz. Ph.D. Assistant Professor of Christian Ethics Pacific School of Religion

David W. Louisell, J.D. Professor of Law University of California at Berkeley

Donald W. Seldin, M.D. Professor and Chairman, Department of

Internal Medicine University of Texas at Dallas

Eliot Stellar, Ph.D. Provost of the University and Professor of Physiological Psychology University of Pennsylvania

Robert H. Turtle, LL.B. Attorney VomBaur, Coburn, Simmons & Turtle Washington, D.C.

The Commission wishes to thank the members of its staff for the valuable assistance provided in the study of research on the fetus and the preparation of this report.

COMMISSION STAFF

Charles U. Lowe, M.D. Executive Director

Michael S. Yesley, J.D. Staff Director

Professional Staff Support Staff

Duane Alexander, M.D. Edward Dixon, J.D. Bradford Gray, Ph.D. Miriam Kelty, Ph.D. Robert Levine, M.D. Barbara Mishkin, M.A. R. Anne Ballard Bernice M. Lee

Mary K. Bell Pamela L. Driscoll Lisa J. Gray Marie D. Madigan Erma L. Pender Susan F. Shreiber

Assistance was also provided by Charles McCarthy, William Dommel and Anthony Buividas.

PREFACE

The National Commission for the Protection of Human Subjects of Biomedical

and Behavioral Research was established by Title II of the National Research Act

(Public Law 93-348) to study the ethical principles underlying biomedical and

behavioral research on human subjects and to make recommendations to the Secretary,

DHEW, and to Congress, for the protection of these subjects. This report was pre-

pared in response to a section of the Act that required the Commission to "conduct

an investigation and study of the nature and extent of research involving living

fetuses, the purposes for which such research has been undertaken, and alternative

means for achieving such purposes" (Section 202 (b)).

This volume, Report and Recommendations: Research on the Fetus, contains

the Commission's Recommendations, the underlying Deliberations and Conclusions,

a dissenting statement and an additional statement by Commission members, and

summaries of materials presented to the Commission. An appendix volume contains

the complete texts of reports and papers prepared for the Commission on the

ethical, legal and medical aspects of research on the fetus and other material

reviewed by the Commission in its deliberations.

CONTENTS

I. The Mandate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

II. The Nature and Extent of Research Involving the Fetus and the Purposes for Which Such Research Has Been Undertaken . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

III. Alternative Means for Achieving the Purposes for Which Research Involving Living Fetuses Has Been Undertaken . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

IV. Legal Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

V. Ethical issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

VI. Views Presented at Public Hearings . . . . . . . . . . . . . . . . . . . . . . 41

VII. Fetal Viability and Death . . . . . . . . . . . . . . . . . . . . . . . . . . . 53

VIII. Deliberations and Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . 61

IX. Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73

Dissenting Statement of David W. Louisell . . . . . . . . . . . . . . . . 77

Statement of Karen Lebacqz, with the Concurrence of Albert R. Jonsen on the First Item . . . . . . . . . . . . . . . . . . . 83

I.

THE MANDATE

The National Research Act (P.L. 93-348) established the National Commission

for the Protection of Human Subjects of Biomedical and Behavioral Research and

gave the Commission a mandate to investigate and study research involving the

living fetus, and to recommend whether and under what circumstances such research

should be conducted or supported by the Department of Health, Education, and Wel-

fare. A deadline of four months after the members of the Commission took office

was imposed for the Commission to conduct its study and make recommendations to

the Secretary, DHEW. The priority assigned by Congress to research involving the

fetus indicates the concern that unconscionable acts involving the fetus may have

been performed in the name of scientific inquiry, with only proxy consent on

behalf of the fetus.

The members of the Commission determined at the outset to undertake a care-

ful study of the nature and extent of research on the fetus, the range of views on

the ethical acceptability of such research, and the legal issues involved, prior

to formulating their recommendations. To this end, the Commission has accumulated

an extensive body of information, held public hearings, questioned a panel of

distinguished ethicists, and conducted lengthy deliberations. In the course of

these activities, the Commission has given close scrutiny to many important ques-

tions that surround research on the fetus, for example: What are the purposes of

research on the fetus? What procedures have been employed in such research? Are

there alternatives to such research? Can appropriate consent to such research be

obtained by proxy? Under what conditions may research be done on a fetus that is

to be aborted, or a nonviable delivered fetus? What review of proposed research

should be required?

In the remainder of Section I, the background and activities of the Com-

mission are summarized, and the definitions used in this report are set forth.

Reports, papers and testimony that were prepared for or presented to the Commis-

sion are summarized in Sections II to VII of this report. The Commission's own

1

statement of its deliberations and conclusions appears in Section VIII, and the

recommendations themselves are set forth in Section IX, together with a state-

ment by a member of the Commission dissenting in part from the recommendations.

Separate views of members of the Commission are set forth in Section X.

The Appendix to the report contains the entire text of the papers and

reports that were prepared under contract to the Commission, and certain other

materials that were reviewed by the Commission during its deliberations.

Legislative Background. The National Research Act contains two provisions

regarding research on the fetus: (1) the mandate to the Commission to conduct

studies and make recommendations to the Secretary, DHEW, (section 202(b)), and

(2) a prohibition, in effect until the Commission has made recommendations, on

"research [conducted or supported by DHEW] in the United States or abroad on a

living human fetus, before or after the induced abortion of such fetus, unless

such research is done for the purpose of assuring the survival of such fetus"

(section 213). These two provisions were drafted by a conference committee

that resolved the differences between the acts originally passed in 1973 by the

House of Representatives and Senate, respectively.

The original House act contained a prohibition against the conduct or

support by DHEW of research that would violate any ethical standard adopted by

the National Institutes of Health or the National Institute of Mental Health.

This provision was perceived as a prohibition of research on the living fetus,

as a result of policy then in force at NIH. In addition, both the House and

Senate acts contained floor amendments explicitly prohibiting the conduct or

support of research on the fetus by DHEW. The House amendment, adopted by a

vote of 354 to 9, proscribed research on a fetus that is outside the uterus and

has a beating heart, while the Senate prohibition applied to research in con-

nection with an abortion. Among other differences between the acts, the House

prohibitions were permanent, while the Senate prohibition was temporary. The

conference committee adopted the Senate approach, imposing a moratorium until

this Commission made recommendations. The moratorium adopted by the conference

committee applies to research conducted on a fetus before or after an induced

abortion of the fetus (except to assure the survival of the fetus); the mandate

for the Commission's study and recommendations applies more generally to research

involving the living fetus.

2

The Commission has reviewed the committee reports (Nos. 93-244, 93-381,

and 93-1148) and the record of the floor debate that led to the passage of the

National Research Act (Congressional Record, daily eds. May 31, 1973; September 11,

1973; June 27 and 28, 1974). Other legislative materials that have been reviewed

include the Hearings on Biomedical Research Ethics and the Protection of Human

Subjects; before the House Subcommittee on Public Health and Environment (Septem-

ber 27 and 28, 1973), and the Hearing on Fetal Research before the Senate Sub-

committee on Health (July 19, 1974).

It is clear from the legislative history that the National Research Act,

as passed by both Houses and signed into law by President Nixon on July 12; 1974,

reflects an acknowledgement by the majority of legislators that the issues sur-

rounding research on the fetus require much study and deliberation before policies

are established regarding support by the Secretary, DHEW. That assignment was

given to the Commission, and this report describes how the assignment was carried

out and the conclusions that were reached.

Existing Codes and Other Relevant Material. To assist its deliberations,

the Commission referred to the following pre-existing codes and other materials

relating to human experimentation:

1. The Nuremberg Code (1946-1949).

2. The Declaration of Helsinki (revised, 1964).

3. The Use or Fetuses and Fetal Material for Research, Report of

the Advisory Group, chaired by Sir John Peel (London, 1972).

4. Protection of Human Subjects: Policies and Procedures, draft

document of the Department of Health, Education, and Welfare

(38 Federal Register No. 221, Part II, November 16, 1973).

5. Protection of Human Subjects: Proposed Policy, Department of

Health, Education, and Welfare (39 Federal Register No, 165,

Part III, August 23, 1974).

(The above documents are included in the Appendix to this report.)

3

Meetings of the Commission. Secretary Weinberger administered the oath

of office to the members of the Commission on December 3, 1974, thereby fixing

the deadline for this report. Section 202(b) of the National Research Act

requires that recommendations of the Commission with respect to research on the

living fetus be transmitted to the Secretary "not later than the expiration of

the 4-month period beginning on the first day of the first month that follows

the date on which all members of the Commission have taken office." This

4-month period expired April 30, 1975.

The Commission conducted seven meetings devoted primarily to the topic

of research on the fetus. These meetings were well attended by the public.

One day of the February meeting was devoted to a public hearing of the views of

persons interested in research on the fetus; oral testimony was given by 23 wit-

nesses, some representing research, religious or other organizations and some

appearing as concerned citizens to express their viewpoints (see Section VI for

summaries of the views presented). At the March meeting, three public officials

testified about the involvement of their respective agencies or offices in

research on the fetus (see Section VI), and the members of the Commission held

a roundtable discussion with several ethicists who had prepared papers covering

a wide spectrum of secular opinion and religious persuasion (see Section V for

summaries of these papers).

Studies and Investigations. The Commission contracted for a number of

studies and investigations. These included a study, undertaken primarily through

review of the literature, of the nature, extent and purposes of research on the

fetus, conducted under contract with Yale University (see Section II); an histor-

ical study of the role of research involving living fetuses in certain advances

in medical science and practice, conducted under contract with Battelle-Columbus

Laboratories (see Section III); and a study utilizing available data to establish

guidelines for determining fetal viability and death, conducted under contract

with Columbia University (see Section VII).

In addition to these studies, papers outlining their views on research on

the fetus were prepared by the following ethicists and philosophers: Sissela Bok

of Harvard University; Joseph Fletcher of the Institute of Religion and Human

Development; Marc Lappé of the Hastings Institute of Society, Ethics, and the

4

Life Sciences; Richard McCormick and LeRoy Walters of the Kennedy Institute for

the Study of Human Reproduction and Bioethics; Paul Ramsey of Princeton Univer-

sity; Seymour Siegel of the Jewish Theological Seminary; and Richard Wasserstrom

of the University of California at Los Angeles (see Section V). Stephen Toulmin,

of the University of Chicago, prepared an analysis of the ethical views that were

presented to the Commission, identifying areas of consensus as well as divergence.

Leon Kass, of Georgetown University, prepared a philosophical paper on the deter-

mination of fetal viability and death (see Section VII). Papers on the legal

issues of research on the fetus were prepared by Alexander M. Capron of the Uni-

versity of Pennsylvania Law School, and John P. Wilson of Boston University Law

School (see Section IV).

(All of the above studies, investigations and papers appear in the Appendix.)

Definitions. For the purposes of this report, the Commission has used the

following definitions which, in some instances, differ from medical, legal or

common usage. These definitions have been adopted in the interest of clarity and

to conform to the language used in the legislative mandate.

"Fetus" refers to the human from the time of implantation until a determi-

nation is made following delivery that it is viable or possibly viable. If it

is viable or possibly viable, it is thereupon designated an infant. (Hereafter,

the term "fetus" will refer to a living fetus unless otherwise specified.)

"Viable infant" refers to an infant likely to survive to the point of

sustaining life independently, given the support of available medical technology,

This judgment is made by a physician.

"Possibly viable infant" means the fetus ex utero which has not yet been

determined to be viable or nonviable. This is a decision to be made by a physi-

cian. Operationally, the physician may consider that an infant with a gesta-

tional age of 20 to 24 weeks (five to six lunar months; four and one-half to five

and one-half calendar months) and a weight between 500 to 600 grams may fall into

this indeterminate category. These indices depend upon present technology and

should be reviewed periodically.

5

"Nonviable fetus" refers to the fetus ex utero which, although it is

living, cannot possibly survive to the point of sustaining life independently,

given the support of available medical technology. Although it may be presumed

that a fetus is nonviable at a gestational age less than 20 weeks (five lunar

months; four and one-half calendar months) and weight less than 500 grams, a

specific determination as to viability must be made by a physician in each

instance. The Commission is not aware of any well-documented instances of sur-

vival of infants of less than 24 weeks (six lunar months; five and one-half

calendar months) gestational age and weighing less than 600 grams; it has chosen

lower indices to provide a margin or safety. These indices depend upon present

technology and should be reviewed periodically.

"Dead fetus" ex utero refers to a fetus ex utero which exhibits neither

heartbeat, spontaneous respiratory activity, spontaneous movement of voluntary

muscles, or pulsation of umbilical cord (if still attached). Generally, some

organs, tissues and cells (referred to collectively as fetal tissue) remain alive

for varying periods of time after the total organism is dead.

"Fetal material" refers to the placenta, amniotic fluid, fetal membranes

and the umbilical cord.

"Research" refers to the systematic collection of data or observations in

accordance with a designed protocol.

"Therapeutic research" refers to research designed to improve the health

condition of the research subject by prophylactic, diagnostic or treatment

methods that depart from standard medical practice but hold out a reasonable

expectation of success.

"Nontherapeutic research" refers to research not designed to improve the

health condition of the research subject by prophylactic, diagnostic or treat-

ment methods.

6

II.

THE NATURE AND EXTENT OF RESEARCH INVOLVING THE FETUS AND THE PURPOSES FOR WHICH SUCH RESEARCH

HAS BEEN UNDERTAKEN

An extensive review of the scientific literature, focusing on a period

covering the last ten years, formed the basis for the Commission's investigation

of the nature, extent and purposes of research on the fetus. The review was con-

ducted under contract with Yale University, Maurice J. Mahoney, M.D., Principal

Investigator. The investigation included an all-language review of published

research, utilizing the MEDLARS computer indexing and search system of the

National Library of Medicine, a review of selected bibliographies and abstracts,

a survey of departments of pediatrics and obstetrics at medical schools in the

United States and Canada to identify current research on the fetus, and a review

of NIH grant applications and contracts since 1972 involving research on the

fetus. In addition, the Food and Drug Administration provided information on

fetal research conducted in fulfillment of its regulations.

For the purpose of summarizing the review, research involving the fetus

has been considered in four general categories.

1. Assessment of Fetal Growth and Development In Utero. Over 600 publi-

cations dealing with investigations of fetal development and physiology were

identified. In general, the purpose of these investigations was to obtain infor-

mation on normal developmental processes, as a basis for detecting and under-

standing abnormal processes and ultimately treating the fetal patient. To this

end, numerous experimental approaches were employed.

Studies of normal fetal growth relied primarily on anatomic studies of the

dead fetus. Studies of fetal physiology involved both the fetus in utero and

organs and tissues removed from the dead fetus. In some instances, this research

required administration of a substance to the mother prior to an abortion or

delivery by caesarean section, followed by analysis to detect the presence of

the substance or its metabolic effects in blood from the umbilical cord or in

tissues from the dead fetus. Information on the normal volume of amniotic fluid

7

at various stages of pregnancy was obtained by injecting a substance into the

fluid and assessing the degree of dilution of that substance; these studies were

performed before abortion, during management of disease states (Rh disease), and

in normal term pregnancies. Similarly, numerous chemicals were measured in amni-

otic fluid to establish normal data.

Research also focused on the development of fetal behavior in utero. Fetal

breathing movements were detected by ultrasound as early as 13 weeks after con-

ception. Fetal hearing was documented by demonstrating changes in fetal heart

rate or EEG in response to sound transmitted through the mother's abdomen. Vision

was inferred from changes in fetal heart rate in response to light shined trans-

abdominally. Increased rates of fetal swallowing after injection of saccharin

into amniotic fluid suggested the presence of fetal taste capability. Observa-

tion of the fetus outside the uterus indicated response to touch at 7 weeks and

the presence of swallowing movements at 12 weeks of gestation.

2. Diagnosis of Fetal Disease or Abnormality. Well over 1000 papers have

been published in the last 10 years dealing with intrauterine diagnosis of fetal

disease or abnormality. Much of this research involved amniocentesis, a proce-

dure in which a needle is inserted through the mother's abdomen into the uterus

and amniotic fluid is removed for analysis. Amniocentesis originally came into

extensive use for monitoring the status of the fetus affected by Rh disease in

the third trimester of pregnancy. Research related to treating Rh disease indi-

cated that the yellow color of the amniotic fluid correlated with the severity

of anemia in the fetus. This color index later was used as an indication of the

need for intrauterine transfusion, a procedure subsequently developed to treat

severely affected infants.

The knowledge that amniocentesis was safe in the third trimester of preg-

nancy, coupled with the demonstration that cells shed from the skin of the fetus

into the amniotic fluid could be grown in tissue culture, led to application of

amniocentesis to detection of genetic disease in the second trimester. The

research conducted in developing this procedure focused first on demonstrating

in fetal cells from amniotic fluid the normal values for enzymes known to be

defective in genetic disease. This research was conducted largely on amniotic

fluid samples withdrawn as a routine part of the procedure of inducing abortion.

8

Once it had been demonstrated that the enzyme was expressed in fetal cells and

normal values were known, application to diagnosis of the abnormal condition in

the fetus at risk was undertaken. The reported research documents a steady pro-

gression in development and application of amniocentesis, so that potentially

over 60 inborn errors of metabolism (such as Tay-Sachs disease) and virtually

all chromosome abnormalities (such as Down's syndrome), as well as the lack of

these defects in the fetus at risk, can be diagnosed in utero, at a time when

the mother can elect therapeutic abortion of an affected fetus.

Research directed at prenatal diagnosis of disease currently focuses on

three main objectives. The first involves attempts to extend diagnostic capa-

bility to additional diseases, such as cystic fibrosis of the pancreas, which

cannot now be detected by amniocentesis. A second approach attempts to detect

fetal cells in the maternal circulation and separate these from maternal cells

for chemical analysis, thus avoiding any risks and difficulties encountered

during amniocentesis. The third direction is the development of fetoscopy, a

process by which an instrument is inserted into the uterus and a sample of fetal

blood is obtained from the placenta under direct visualization. The blood sample

is analyzed to diagnose disorders such as sickle cell disease or thalassemia

which cannot be detected by amniocentesis. The time needed for laboratory analy-

sis following fetoscopy is markedly shorter than the four to six weeks required

to obtain tissue culture results in amniocentesis. Fetoscopy also permits visual

examination of the fetus for external physical defects.

Because of the unknown but theoretically significant risks that remained

following animal studies, fetoscopy was developed selectively in women undergoing

elective abortion. The first clinical applications have been reported in recent

months: three fetuses at risk for beta-thalassemia, whose mothers were seeking

abortion to avoid the possibility of having an affected child, were diagnosed

as free of disease following fetoscopy. All three have been born and are normal.

Research has also been directed at the identification of physical defects

in the developing fetus. The most handicapping defects are those of the neural

tube (anencephaly or meningomyelocele). Initial research efforts were devoted

to developing X-ray techniques to view the fetus for these defects by injection

of radiopaque substances into amniotic fluid (amniography or fetography). These

studies primarily involved women having a family history of neural tube defects

9

and whose fetuses were consequently at increased risk. More recently, elevated

levels of alpha-fetoprotein in amniotic fluid (or maternal blood) were found to

be associated with neural tube defects, and may serve as a screening test for

these disorders. Ultrasound has come into use to determine internal and external

structural detail of the developing fetus and thereby to detect anencephaly,

meningomyelocele, and even congenital heart disease.

Amniocentesis also opened another area of fetal research: the assessment

of fetal lung maturity. Studies of normal amniotic fluid in the last trimester

of pregnancy provided an indication that increased concentrations of lecithin

relative to sphingomyelin reflect maturation of the fetal lung; infants with

mature lungs did not develop respiratory distress. This predictive test (the

L/S ratio) was applied when women went into premature labor, or when induced

delivery was indicated due to Rh disease or maternal diabetes, to assess the risk

that the delivered infant would develop respiratory distress. When the lungs

were immature, delivery could be delayed, depending on the relative risks of

intrauterine versus extrauterine life. In the last three years, attempts to

induce fetal lung maturation by administration of corticosteroids to the mother

have added a new dimension to this clinical situation. Following animal studies

indicating that this procedure was safe and effective, human studies were under-

taken intending to benefit the fetus involved. Results reported to date suggest

that the procedure is successful, but studies of possible long-term side effects

of this intrauterine therapy are continuing.

Assessment of fetal well-being is another goal of fetal research. Ultra-

sound has been used to assess fetal size and gestational age, and to monitor

fetal respiratory movements, certain types of which have been found to indicate

fetal distress. Studies of hormones, metabolic products and chemicals in amni-

otic fluid (and in maternal blood and urine) identified numerous substances asso-

ciated with either abnormalities of fetal growth or with fetal distress. In the

last decade, monitoring the fetal heart rate and sampling fetal scalp blood

during labor developed from research techniques to clinical application for indi-

cation of fetal distress.

3. Fetal Pharmacology and Therapy. Over 400 publications in the last

10 years involving fetal pharmacology were identified in the literature search;

10

less than 20 percent of these included research on the living fetus. Of the

latter studies, the majority were coincidental studies conducted as an adjunct

to clinically accepted procedures. For example, the largest category encompassed

studies of transplacental drug movement or effects on the fetus of analgesic or

anesthetic agents given to the mother during labor and delivery.

The research techniques employed in investigations of this type included

antepartum transfusion of the fetus with blood containing drugs, and administra-

tion of drugs or agents to the mother for the therapeutic research reasons. The

ensuing studies involved assessment of effects on the fetal electrocardiogram,

determination of fetal movements or structures by ultrasound, amniotic fluid

sampling, scalp or umbilical cord blood sampling, and studying placental passage

and fetal distribution patterns in tissues of the dead fetus. The studies were

conducted either prior to abortion or in normal pregnancies, usually at the

time of delivery.

In general, studies to determine the effects of a drug on the fetus were

retrospective, involved the fetus incidentally or after death, or involved the

infant, child or adult. Thus, all studies of the influence of oral contracep-

tives or other drugs on multiple births or congenital abnormalities were retro-

spective. Study of the effects on the fetus of drugs administered to treat

maternal illness during pregnancy (including anticonvulsants, antibiotics, hor-

mones and psychopharmacologic agents) in which the fetus was an incidental par-

ticipant, were also largely retrospective. Studies of effects on the fetus and

newborn infant of analgesic and anesthetic agents given at delivery also involved

the fetus incidentally, but were conducted prospectively. Recently attempts were

made to focus prospective pharmacologic studies of antibiotics intentionally,

rather than incidentally, on the fetus. Different antibiotics were administered

to pregnant women before abortion to compare quantitative movement of these

agents across the placenta, as well as absolute levels achieved in fetal tissues.

The results served as a guideline for drug selection to treat intrauterine infec-

tions, particularly syphilis. Studies conducted on the dead fetus after abortion

showed the clear superiority of one drug over the other.

In addition to assessing effects of drugs on the fetus and measuring pla-

cental transfer of drugs, fetal pharmacologic research included attempts to

11

modify drug structures so that they will or will not cross the placenta to

affect the fetus. Such research also included study of the effects of certain

drugs (such as phenobarbital or corticosteroids) in inducing enzyme activity in

the fetus (to prevent hyperbilirubinemia or speed fetal lung maturation and pre-

vent respiratory distress syndrome).

Effects on the fetus of live attenuated virus vaccines administered to

the mother were also examined. Preliminary testing of rubella vaccine in mon-

keys indicated that the vaccine virus did not cross the placenta. In contrast,

studies on women requesting therapeutic abortion showed clearly that the vaccine

virus did indeed cross the placenta and infect the fetus, indicating the danger

of administering the vaccine during pregnancy. Similarly, a study conducted with

mumps vaccine virus showed that the virus infected the placenta, but not the fetus.

Attempts at fetal therapy in utero, in addition to blood transfusion for

Rh disease and corticosteroid administration to speed fetal lung maturity, were

conducted recently as an adjunct to amniocentesis. Examples of this type of

fetal therapy include the administration of hydrocortisone to the fetus in utero

to treat the adrenogenital syndrome, maternal dietary therapy for fetal galacto-

semia, and administration to the mother of large doses of vitamin B 12 to treat

fetal methylmalonic acidemia.

4. Research Involving the Nonviable Fetus. The quantity of research on

the nonviable fetus ex utero has been small; much of such research included the

nonviable fetus only at the extreme end of the spectrum of studies of premature

infants. Such studies included measurements of amino acid levels in plasma of

infants with intrauterine malnutrition, administration of bromide to measure

total body water in low birth weight infants, and the study of hemoglobin in

blood from the umbilical cord as an indicator of fetal maturity. The purpose of

this research was to gain information that could be of benefit to other fetuses

and infants.

Research was also conducted involving the nonviable fetus during abortion

by hysterotomy but before the fetus and placenta were physically removed from

the uterus. A study conducted in the United States reported the feasibility of

delivering a portion of the umbilical cord from the uterus and using it as a site

12

for drug administration and blood sampling. Another study, this one undertaken

in Finland, employed the technique to infuse noradrenaline via the umbilical

vein; study of metabolites subsequently obtained demonstrated the functional

maturity of the fetal sympathetic nervous system. Several studies in Sweden used

similar techniques: radiolabeled chemicals were administered to the fetus via

the umbilical vessels, and metabolites were then studied in the umbilical vein

and, following completion of the abortion, in the fetus. In another Finnish

study, arginine and insulin were injected into blood vessels of eight fetuses

(450-600 grams) with the placenta attached to the uterus, and blood samples were

taken from the umbilical cord to assess fetal endocrine regulation of glucose

metabolism. These studies were conducted solely to gain information on fetal

metabolism for the benefit of other fetuses and infants.

The nonviable fetus was the subject of research to develop a life-support

system ("artificial placenta") for sustaining very small premature infants, as

well as to obtain data on normal fetal physiology. Some of this life-support

system research was conducted only with larger infants (viable by weight criteria)

who had failed on respirators and were tried on experimental systems as an ulti-

mate therapeutic effort to achieve survival. Of the published studies with

clearly nonviable fetuses, one was conducted in the United States. Published in

1963, this research involved 15 fetuses, obtained following therapeutic abortion

at 9-24 weeks gestational age. The fetuses were immersed in salt solution con-

taining oxygen at extremely high pressure, in an attempt to provide oxygen for

the fetus through the skin. The longest survival was 22 hours. In an earlier

study in Scandinavia, seven fetuses weighing 200-375 grams, from both spontaneous

and induced abortions, were perfused with oxygenated blood through the umbilical

vessels. Longest survival was 12 hours. A third study, conducted in England,

utilized a similar method and included eight fetuses obtained following hyster-

otomy abortion and weighing 300-980 grams. Longest survival was 5 hours. No

other studies of this type involving nonviable fetuses were found in the litera-

ture review.

Studies of fetal physiology conducted on the delivered fetus utilized

several experimental approaches. In a study conducted in Sweden, the intact

fetal-placental unit obtained by hysterotomy abortion was removed and utilized

for perfusion studies. A study performed in England involved cannulating the

13

carotid and umbilical arteries of the aborted fetus and measuring fetal glucose

levels in response to administration of growth hormone. Four fetuses from hys-

terotomy abortions at 16-20 weeks gestation were perfused via the umbilical ves-

sels in a study in Scotland which demonstrated that the fetus could synthesize

estriol independent of the placenta. A similar study by the same investigators

involving six fetuses demonstrated that the 16-20 week fetus could synthesize

testosterone from progesterone. To learn whether the human fetal brain could

metabolize ketone bodies as an alternative to glucose, brain metabolism was iso-

lated in eight human fetuses (12-17 weeks gestation) after hysterotomy abortion

by perfusing the head separated from the rest of the body. This study, conducted

in Finland, demonstrated that the human fetus, like previously studied animal

fetuses, could modify metabolic processes to utilize ketone bodies.

These studies of the nonviable fetus represent the total number reported in

the world scientific literature, as well as could be ascertained from review of

the most comprehensive bibliographic search ever undertaken of research involving

the human fetus. The total number of citations involving fetal research was well

in excess of 3000; the reports of research on the nonviable fetus that were found

numbered less than 20. Certainly some reports of such research may have been

missed even by this thorough review, but it is safe to conclude that the amount

of research conducted on the nonviable fetus has been extremely limited. Of the

principal investigators conducting this type of research, three were from the

United States; two of these investigators conducted their research abroad. The

only research conducted in the United States on the nonviable fetus ex utero was

the study involving attempts to develop an artificial life-support system. The

literature survey disclosed no reports of research conducted in the United States

on the nonviable fetus intended solely to obtain information on normal physiologic

function.

In summary, research involving the fetus includes a broad spectrum of

studies of the fetus both inside and outside the uterus. The research may be as

innocuous as observation, or involve mild manipulation such as weighing or mea-

suring, or more extensive manipulation such as altering the environment, admin-

istering a drug or agent, or noninvasive monitoring. Diagnostic studies may

involve sampling amniotic fluid, urine, blood, or spinal fluid, or performing

14

biopsies. The most extensive or invasive procedures include perfusion studies

and other attempts to maintain function.

The extent of research on the fetus is reflected by the more than 3000

citations included in the literature review of such research. Most involved the

fetus in utero; less than 20 articles involved the nonviable fetus.

The purposes for which research on the fetus has been undertaken include

obtaining knowledge of normal fetal growth and development as a basis for under-

standing the abnormal; diagnosing fetal disease or abnormality; studying fetal

pharmacology and the effects of chemical and other agents on the fetus, in order

to develop fetal therapy; and developing techniques to save the lives of ever

smaller premature infants.

15

III.

ALTERNATIVE MEANS FOR ACHIEVING THE PURPOSES FOR WHICH RESEARCH INVOLVING LIVING FETUSES

HAS BEEN UNDERTAKEN

In the development of new medical procedures or drugs to be employed in

the treatment of humans, research is usually initiated with animal models, which

are used until probable effectiveness and low degree of risk are determined.

Ultimately, it becomes necessary to conduct the research on humans, since initial

human applications are experimental regardless of the amount of preceding animal

research. In some instances, pertinent animal models may not exist or may have

certain limitations, so that studies on humans begin at a relatively early stage.

In all instances, however, the question may be asked whether studies on humans

began at an appropriate time, or whether the information that was required could

have been obtained using alternative research means, i.e., studies on animal

models.

The broad nature of the survey of the nature and extent of research on

the fetus (Section II) did not permit detailed evaluation of alternative means.

Therefore, the Commission contracted with Battelle-Columbus Laboratories to con-

duct a more intensive analysis of this issue in connection with four advances in

which research on the fetus played a part. The Battelle report to the Commission

traces the historical development of (1) rubella vaccine, (2) the use of amnio-

centesis for prenatal diagnosis of genetic defects, (3) the diagnosis and treat-

ment, as well as prevention, of Rh isoimmunization disease, and (4) the management

of respiratory distress syndrome. The study identifies pertinent animal research

that was conducted and attempts to assess whether the human research was necessary

and appropriate, or whether animal models could have been substituted. Finally,

the study evaluates the likelihood that the advance would have been achieved if

all research on the fetus, both therapeutic and nontherapeutic, had been pro-

hibited. In preparing the report and analysis, extensive bibliographies on each

topic, prepared by staff of the National Library of Medicine, were utilized. In

addition, a number of scientists whose research had been of greatest importance

to the advances were interviewed.

17

1. In the case of congenital rubella syndrome, descriptions of the condi-

tion (which comprises congenital heart disease, cataracts, deafness and mental

retardation) and its etiology (maternal rubella infection during pregnancy) were

drawn from research on the living child and material from dead fetuses. Atten-

uation of the rubella virus for vaccine purposes was accomplished in tissue cul-

ture using nonhuman cells. Vaccine trials were conducted on adults and children.

The vaccine was found safe and effective, and it was licensed in 1969, 28 years

after the congenital rubella syndrome was first described.

No research on the living human fetus was required to develop the vaccine.

A question remained, however, as to the safety of administering the vaccine during

pregnancy or to women in the child-bearing years. Should a pregnant woman, with-

out immunity to rubella, be vaccinated to prevent the risk to the fetus that would

ensue if she contracted natural rubella? Some experimental animal models for the

rubella condition had been developed, the rhesus monkey being the closest one to

the human. Accordingly, pregnant monkeys were inoculated with either rubella

virus or the vaccine virus. Subsequent study showed that five of six monkey

fetuses whose mothers received slightly attenuated rubella virus were infected,

but none of the six monkey fetuses whose mothers received vaccine virus was infec-

ted. Thus, the animal model suggested that the vaccine virus did not cross the

placenta and was safe to administer during pregnancy, although other vaccine

viruses were known to cross the human placenta.

Human studies were then undertaken. Because of the potential risk to the

fetus, women requesting therapeutic abortion were employed as subjects. These

volunteers received the vaccine and underwent the abortion 11 to 30 days later.

Examination of tissues from the dead aborted fetuses showed that, in contrast to

the results in monkeys, the vaccine virus did cross the human placenta and infect

the fetus. On the basis of this research involving the fetus in anticipation of

abortion, as well as subsequent reports of damage to the fetus following accidental

rubella vaccination during pregnancy, administration of rubella vaccine to preg-

nant women or women who might become pregnant within 60 days of vaccination is

proscribed.

Two alternatives to the planned testing of rubella vaccine on pregnant

women in anticipation of abortion can be considered. First, more extensive ani-

mal testing of the vaccine could have been conducted. The usefulness of such a

18

procedure, however, would be questionable. Based on prior experience with the

inconsistencies of placental passage of any agent, the human situation would

remain unknown after any amount of animal testing. Testing in the human is

still required even after negative results in animal models, with the same

safeguards as if no animal testing had been conducted.

The second alternative would be to wait for the accidental vaccination

of pregnant women and observe the outcome. This in fact occurred in several

instances after the planned testing. The women involved, who had wanted preg-

nancies, elected instead to terminate their pregnancies by abortion due to the

risk to the fetus, and studies of tissue from the dead fetuses confirmed that

they had been infected by the virus. Thus, the effect in humans could have been

learned in this instance by retrospective research. At issue here in the selec-

tion of alternatives is the question whether it is preferable to proceed by

design with women planning abortions, or to work retrospectively with women who

desire pregnancy but were accidentally vaccinated.

2. The use of amniocentesis (removal of amniotic fluid via a needle

inserted into the uterus through the mother's abdomen) as a clinical procedure

dates from 1882, when it was introduced as a treatment for polyhydramnios (excess

accumulation of amniotic fluid). There is no evidence that animal studies were

conducted prior to that time, and comparatively little research has been done on

amniocentesis as a procedure apart from its applications. The Battelle study of

amniocentesis thus involved evaluation of the uses to which the procedure has

been put, as well as alternative means for developing the procedure. Amniocen-

tesis has found application in three main areas of research: prenatal diagnosis

of genetic disease, diagnosis of Rh disease, and assessment of fetal maturity

related to respiratory distress syndrome. Its use in the latter two areas will

be discussed in parts 3 and 4 of this section.

Two lines of research provided impetus for prenatal diagnosis of genetic

disease: development of the technology for tissue culture and identification of

the sex chromatin as an indicator of sex in single cells. In 1955 it was shown

that fetal sex could be predicted from the sex chromatin pattern of amniotic

fluid cells. Application of this technique to prenatal detection of sex-linked

disorders was first reported in 1960. Rapid progress in tissue culture research

19

led to success in culturing fetal amniotic fluid cells in 1966, intrauterine

diagnosis of a chromosome abnormality in 1967, and the first intrauterine

diagnosis of metabolic disorders using cultured amniotic fluid cells in the

following year. Research in this area steadily expanded as chromosomal and

metabolic disorders were added to the list of conditions diagnosable in utero.

At present, virtually any chromosomal anomaly and potentially over 60 metabolic

disorders can be detected prenatally by amniocentesis. The possibility of

diagnosis and selective abortion of abnormal fetuses has enabled the birth of

normal children to families that otherwise would not have risked pregnancy,

and has permitted families to avoid the impact of the birth of a defective or

doomed child.

All research to detect genetic defects involved the living human fetus.

Much of it utilized amniotic fluid obtained in the normal course of abortion, in

order to ascertain normal values. Such research was obviously nonbeneficial for

the fetuses involved. Only research conducted on women at risk for having a

fetus with the disorder in question could be considered beneficial, in that

many of these women desired an abortion unless it could be shown that the fetus

would be normal.

An alternative means to develop the procedure of amniocentesis would have

been to conduct more extensive animal research. Animal models have numerous

limitations with regard to amniocentesis, however, including shape of the pelvis,

size and shape of the uterus, number of fetuses present (which confounds cell

analysis), and the marked irritability of the uterus in many species such that

even slight manipulation induces abortion, fetal resorption or congenital mal-

formations. Recently some animals have been found in which amniocentesis can be

performed, but even in these it is difficult in midpregnancy, when it must be done

for effective intrauterine diagnosis of genetic defects.

While animal models might have been utilized more extensively in develop-

ing the technique of amniocentesis, there is no alternative to human experimen-

tation for the purpose of developing the diagnostic tests for genetic metabolic

disorders used with amniocentesis. The conditions are unique to the human species.

Only by study of cells in amniotic fluid from pregnant humans, both normal and

those at risk for genetic disease in the fetus, was it possible to assess whether

the genetic defect was expressed in these cells, and to determine the normal and

20

abnormal values for the responsible enzymes in the cells as the basis for pre-

natal diagnosis. This research utilized only amniotic fluid and the fetal cells

in it, and thus was not invasive of the fetus. In the early stages of developing

the technique, however, the possible risks to the fetus were greater than those

for many invasive procedures.

3. The history of Rh isoimmunization disease encompasses the description

of the disorder, determination of its cause, initiation of successful treatment,

and development of effective prevention, all within four decades. Character-

ization of this disorder, which combines hemolytic anemia, jaundice, and intra-

uterine death or (if delivered) severe brain damage, was accomplished in the

1930's from study of autopsy material and newborn infants. Research on blood

groups, utilizing both human and animal material, led in 1941 to the demonstra-

tion from studies of mothers and newborns that Rh sensitization in an Rh negative

mother to an Rh positive fetus produced hemolytic anemia in the fetus. In 1945,

treatment of affected newborn infants by exchange transfusion was initiated and

mortality began to decline.

Use of amniocentesis was introduced in 1956 to obtain amniotic fluid which

provided an indicator of how severely the fetus was affected and, late in preg-

nancy, whether labor should be induced to enable treatment of the fetus outside

the uterus. In 1963, treatment of the severely affected fetus by intrauterine

blood transfusion was initiated, resulting in a 60 percent reduction of the

stillbirth rate for affected infants. Ongoing studies of the etiology of the

disease, using pregnant women, provided indications that sensitization of the

mother usually occurred at the time of delivery of her first Rh positive infant,

when a large volume of fetal Rh positive cells entered the mother's circulation.

As the result of research conducted largely with prisoners, a vaccine was devel-

oped to prevent this sensitization. Trials of the vaccine, administered to women

after delivery, began in 1964. Results indicated virtually complete effective-

ness, and the vaccine (RhoGam) became commercially available in 1968.

Research on the fetus played no part in developing the RhoGam vaccine, but

such research was essential in demonstrating the basic cause of the disease and

in developing methods for prenatal diagnosis and treatment. All significant

research on the fetus related to Rh disease was conducted on mothers and fetuses

21

at risk for the disease, and can be categorized as beneficial research. The

size of the benefits achieved may be appreciated by reviewing statistics related

to the disorder. Approximately 12 percent of couples in the United States are

at risk for having an affected infant. Nearly 25,000 infants could be affected

yearly. Since initiation of exchange transfusion, neonatal mortality of affected

infants has dropped to about 2.5 percent. Intrauterine transfusion has reduced

the annual number of stillbirths due to the disease from 10,000 to less than half

that number. The entire amount of money used to support Rh disease research from

1930 through the successful development of the vaccine in 1966 is the equivalent

of the present cost to society for lifetime care of six children irreparably brain

damaged by the disease.

Limited animal models were available for study of Rh disease and were

utilized in some instances. Intrauterine transfusion, for example, was first

conducted on animals. Extensive research has been conducted to develop an animal

model of the actual disease, but the hamadryas baboon is the only species that

has been found in which the disease is sufficiently similar to the condition in

man for the animal to serve as a useful model. The limitations of animal models

and the urgency of developing a treatment for fetuses otherwise likely to die led

physician researchers to attempt experimental therapy with favorable risk/benefit

ratio in human subjects. In these instances, the risk of not doing the research

was approximately 50 percent intrauterine death; in the face of such odds, even

such a hazardous experimental therapeutic procedure as intrauterine transfusion

was considered acceptable.

4. Respiratory distress syndrome (RDS) is a major cause of infant mortal-

ity. In the United States approximately 40,000 cases occur annually; 95 percent

of these cases are premature infants, and overall mortality is in excess of

25 percent. Study of the development of advances related to this condition

revealed a picture of frequent interaction of animal model and clinical studies

involving the living human fetus in the third trimester. In addition, advances

in therapy were achieved from research involving affected premature infants.

The key experimental work elucidating the basic cause of the condition

involved study of the lungs of deceased infants who died of RDS or other causes.

This research indicated that lungs of infants with RDS lacked a chemical

22

(surfactant) which acted to keep open the smallest air passages in the lung;

surfactant was present in the lungs of unaffected infants. Subsequent studies,

again relying primarily on autopsy material, delineated the biochemistry of

surfactant, and it was suggested that amniotic fluid might provide an indicator

of the presence of surfactant. Studies were then conducted of amniotic fluid

obtained at various stages in the last trimester of pregnancy, solely to learn

the normal values of the phospholipid components of surfactant; this research

was nonbeneficial for the fetuses involved. Results indicated that a marked

increase in the content of lecithin relative to sphingomyelin in amniotic fluid

correlated with the appearance of surfactant in the fetal lung, and indicated

that the lungs were mature enough that the fetus, if delivered, would probably

not develop RDS. The report of these studies in 1971 strongly influenced

obstetric management of premature labor and diabetic pregnancy, by providing an

index of the time when delivery could proceed with minimum risk of RDS.

Another line of research quickly had an impact on RDS management. Animal

studies in the 1950's showed that steroids were capable of inducing enzyme

activity in the fetus. Studies involving the pregnant woman and the living fetus

in 1961 demonstrated that cortisone crossed the human placenta. Animal studies

in the late 1960's and early 1970's indicated that corticosteroids could induce

enzymes and thereby increase surfactant in fetal lungs. In the species studied

(lambs, rabbits and rats) the steroids did not cross the placenta and had to be

administered directly to the fetus. Based on the previous demonstration that

steroids crossed the human placenta, and later clinical studies of mothers

receiving steroid therapy during pregnancy that had not suggested any ill effects

on the fetus, clinical trials were initiated in pregnant women at risk of having

infants affected by RDS. The results obtained to date indicate that corticoster-

oids are highly effective in preventing RDS, without undesirable side effects.

Although the treatment remains experimental, it holds promise for markedly

reducing the incidence of RDS.

The interplay between animal and human studies was essential in achieving

the advances in clinical management and prevention of RDS. Relevant animal

models were used when available, and although no extensive search for an animal

model was evident before the human steroid trials, the research appeared to be

a logical and carefully planned step undertaken to provide therapy for a con-

dition of high risk to the fetuses treated.

23

The following conclusions are drawn from the Battelle study:

A. Animal models were utilized extensively, but adequate and appropriate

models were not always available when they were needed. In some instances little

or no animal research preceded human studies. In other instances intensive

searches for animal models were undertaken (as in Rh disease), but investigators

appear to have been reluctant to postpone therapeutic research until an animal

model was found.

B. Investigators generally proceeded to clinical trials characterized

by very high ratios of benefit to risk.

C. A total ban on all research on the fetus, or postponement of such

research until more appropriate and exact animal models were sought and studied,

would probably have significantly delayed or halted indefinitely the progress in

three of the four areas that were analyzed. Only development of the rubella

vaccine could have progressed unimpeded.

A more limited ban would have had less effect, depending on the nature and

scope of the prohibitions imposed. For example, a ban only on nontherapeutic

research on the fetus would not have affected research on Rh disease, but would

have sharply curtailed research with amniocentesis, due to the resulting inability

to determine normal values for abnormal enzymes in metabolic disorders. The

research which developed L/S ratios, used in RDS diagnosis, might have been

possible making use of fluid obtained during caesarean sections or in Rh disease

studies. A selective ban on research before or after induced abortion would

clearly have permitted the L/S ratio research for RDS diagnosis, but could still

have severely curtailed development of amniocentesis for prenatal diagnosis by

making ascertainment of normal values extremely difficult. A ban on invasive

research on the fetus would have permitted development of amniocentesis, although

the risks to the fetus from this noninvasive procedure were potentially greater

than those from many invasive procedures.

24

IV.

LEGAL ISSUES

Papers on the legal issues involved in research on the fetus were prepared

for the Commission by Professor Alexander M. Capron, University of Pennsylvania

Law School, and Assistant Dean John P. Wilson, Boston University School of Law.

Both papers are structured, at least in part, according to categories of research,

that is, whether the research is therapeutic or nontherapeutic, whether the fetal

subject is viable, nonviable or dead, and whether it is inside or outside the

uterus. The interests of the fetus at different stages of development are bal-

anced against the interests of other parties, and the protection of fetal inter-

ests is addressed in discussion of appropriate consent requirements. A summary

of both papers follows.

The Dead Fetus. The Uniform Anatomical Gift Act (UAGA), which has been

adopted in all fifty states and the District of Columbia, permits research on

the dead fetus and the products of conception, provided consent has been given

by either parent and the other parent has not objected. Professor Capron states

that the UAGA should be read in the context of common law requirements on consent;

thus, the authorization should be "informed" and "voluntary." In the latter

regard, consent should not unnecessarily be sought immediately before or after

an abortion. Dean Wilson suggests that it is wise to require the consent of

both parents.

Aside from the UAGA, Professor Capron points out that the statutes of

five states presently impose varying degrees of restriction on research on the

dead fetus (Massachusetts, South Dakota, Illinois, Indiana, and Ohio); all of

these restrictions apply only to the products of induced and not spontaneous

abortions. Other laws that might affect research on the dead fetus are the grave

robbing statutes, which would apply only when the consent required by the UAGA

has not been obtained. As a matter of medical practice, however, maternal con-

sent is not generally sought for postabortion examinations. (Both authors note

and discuss a pending Massachusetts case.)

25

Professor Capron states that the various state laws on death certification

provide little guidance on the question of defining death with respect to the

fetus. Such laws do, however, introduce another complication by recognizing

different categories requiring certification. (Other reports prepared for the

Commission suggest medical criteria for determining fetal death; see Section

VII of this report.)

The Viable Infant. Research on the viable infant is discussed at length

by Professor Capron. He states that therapeutic research on a viable infant,

whether or not there has been an induced abortion, is generally sanctioned under

criminal and civil law. The law is presently unsettled with respect to nonthera-

peutic research, and, as a practical matter, the exercise of caution in intro-

ducing any risk is indicated. The recently enacted fetal research statutes have

probably not altered the common law with respect to research on the viable infant

after induced abortion, i.e., therapeutic research may be conducted. In the

absence of a special statute, the protection afforded the viable infant attaches

only after it is in fact ex utero.

Although the interests of the viable infant do not depend on the manner in

which it came to be alive ex utero, Professor Capron points out that this might

be relevant to the issue of appropriate consent to involvement of the infant in

research. The question is whether the decision to abort should disqualify the

parents (or at least the mother) from exercising further control after the infant

is alive ex utero. The argument for disqualification has an obvious rationale

in conflict of interest, but it faces at least three problems: (1) Since the

Supreme Court has declared in Roe v . Wade that women have a constitutional right

to abortion, basing maternal disqualification on the exercise of that right may

be an unconstitutional penalty. (2) Since the abortion itself is legal, the

fetus is not thereby deprived of any rights which the parents were obliged to

protect. (3) The decision to abort does not necessarily cast the woman as being

irrevocably opposed to the rights of the fetus, since the mother's decision was

based on the erroneous assumption that there would be no live issue from the

pregnancy. Professor Capron suggests that rather than presumptive disqualifica-

tion in all cases, judicial proceedings may be an appropriate forum for balancing

the rights of all concerned, and that it would be preferable to presume that

26

parents retain control over a viable infant. Certain states, however, have

written into their abortion statutes some form of parental forfeiture of rights

(Louisiana, Missouri, Montana, Kentucky, Indiana, South Dakota).

Dean Wilson suggests that, at least with respect to therapeutic research,

the power of consent should not be removed from a mother and father because they

are minors. Also, he expresses the belief that only therapeutic research should

be conducted on the viable infant.

The Fetus In Utero. Although the fetus does not achieve the interests of

a full person until live birth, it is not entirely without protection while still

in utero. Professor Capron points out that the criminal law in various states,

with expansions under civil law, recognizes interests of the fetus in utero in

two ways of possible relevance to research. First, there are some recent stat-

utes seeking to safeguard the fetus in utero against life-threatening intentional

injury, and some older statutes that depart from the common law by prohibiting

"feticide." It is unlikely that the older statutes would apply to research on

the fetus, since the element of intent to do harm would be missing. All of these

statutes must, of course, be examined in the light of Roe v . Wade .

Second, interests of the fetus in utero are recognized in the criminal

law by protecting the fetus against injuries which cause its death or impairment

after it is born alive. The effect of such protection is to put pressure on

those involved to assure that the abortion is "effective." Thus, Professor

Capron suggests, the law may be recognizing, not fetal interests, but the inter-

ests of human beings, after birth, not to suffer because of culpable acts of

other persons.

In some jurisdictions, Professor Capron finds that the civil law recognizes

a broader fetal interest in protection against harm in utero. The courts in at

least 21 states have recognized a cause of action for injuries to a viable fetus

that lead to its stillbirth. Once the fetus is viable, Professor Capron states,

the decision in Roe v . Wade does not appear to be an absolute bar to holding that

the fetus and its parents have an interest in its potentiality for life.

If the fetus is in fact born alive, the protection under civil law is even

broader, with no importance being attached to the question whether the injury

27

that causes impairment or subsequent death occurred before or after viability.

(Professor Capron expresses his disagreement with the argument that subsequent

live birth is not a necessary element in court decisions regarding the vesting

of property interests.)

Finally, if the fetus is both injured and dies before it is viable, recov-

ery for its wrongful death has not been allowed under civil law.

Dean Wilson expresses the opinion that there should be no difference in

the rights accorded to the fetus in utero before or after viability, and only

therapeutic research or nontherapeutic research that imposes no risk should be

permitted in both cases. He would apply the same conditions to research in

anticipation of abortion. As grounds for protecting the fetus in utero before

viability, he suggests that research on such a fetus might have a brutalizing

effect on society as a whole.

With respect to the question of consent to research on the fetus in utero,

Professor Capron holds that if the fetus is viable, it is in approximately the

same position as a viable infant, i.e., consent by the parents to therapeutic

research would be appropriate, but nontherapeutic research that introduces genu-

ine risk should not be undertaken at all. If the fetus is not yet viable,

Professor Capron discerns two difficult consent issues: (1) Should there be a

separate consent, in addition to that of the mother, when the research is

directed at the fetus? A possible answer is that the mother's right of decision

to destroy the fetus, recognized by Roe v . Wade , includes a right to permit the

fetus to be used in research that is less harmful than total destruction and is

done for legitimate scientific reasons. (2) Can the consent of the mother to

participate in (nontherapeutic) research directed at the fetus be tied to an

agreement to abort? Without such an agreement, parties such as the father and

state welfare officials may have grounds to insist that their interests in the

potential child be protected. On the other hand, an agreement to abort would

probably be unenforceable.

Professor Capron sees no clear answer to the question of appropriate con-

sent to research on the fetus in utero before viability. He suggests a partial

solution along the lines of the Massachusetts fetal research statute, which pro-

vides that research may take place when the fetus is not the subject of a planned

28

abortion and that a statement, signed by the woman, that she is not planning

an abortion supplies conclusive evidence on the point. Such an arrangement

would not be immune from attack in light of the Roe v . Wade decision, but it

would raise fewer questions, Professor Capron states, if it were a condition of

government funding.

In accordance with his views concerning permissible research on the fetus

in utero, Dean Wilson expresses the belief that the woman should be permitted to

consent only to therapeutic research and nontherapeutic research that imposes no

risk.

The Nonviable Fetus Ex Utero. Professor Capron notes that the law gener-

ally does not distinguish between viability and nonviability after birth. Full

protection as a person is given, notwithstanding that immaturity may preclude

the nonviable fetus from having an independent existence. Professor Capron sug-

gests that legislative consideration of the concept of viability as currently

understood might lead to distinctions being made on that basis.

With respect to consent, Professor Capron states that the same rules would

apply for therapeutic research on the viable fetus as for such research on the

viable infant. For nontherapeutic research on the nonviable fetus, he suggests

that judicial review might be appropriate.

29

V.

ETHICAL ISSUES

Eight ethicists and philosophers prepared for the Commission papers out-

lining their views on research on the fetus. Summaries of each of these papers

follows:

Sissela Bok, Ph.D.

Dr. Bok identifies two lines of argument opposed to research on the

fetus: (1) the fetus is a person and, consequently, research without its con-

sent and not for its benefit is an assault upon its humanity; and (2) research

on the fetus will lead society to condone research on other categories of the

defenseless. Dr. Bok answers these arguments and concludes that, in order to

seek knowledge not otherwise obtainable, research should be permitted at early

gestational stages, provided careful safeguards are utilized.

The first argument is countered by a presentation and discussion of four

reasons for protecting humans from harm: (1) the victim's anguish, suffering

and deprivation of continued experience of life; (2) the brutalization of the

agent; (3) the grief of those who care about the victim; and (4) the establish-

ment of a pattern that ultimately will harm all of society. Dr. Bok contends

that none of these reasons apply in the early stages of gestational life.

The second argument against research on the fetus advances the last

reason for protecting humans from harm as crucial even with respect to research

in the first weeks of gestational life. Dr. Bok asserts that no data have been

developed to support the applicability of the fourth reason to research on the

fetus, and that, in any case, safeguards can be developed to prevent the alleged

sequential abuses.

Since the fetus is not a person, consent on its behalf is unnecessary.

However, maternal consent should be obtained, even for research following

abortion, in deference to the woman's sensitivities.

31

Dr. Bok concludes that since the means are defensible and the end is desir-

able, research on the fetus should be permitted during the first 18 weeks of ges-

tational age and when the fetus is under 300 grams in weight. These limits pro-

vide a margin of safety to prevent accidental experimentation on a viable fetus.

Only therapeutic research on a fetus older than 18 weeks or more than 300 grams

in weight should be permitted.

Dr. Bok would permit research on a fetus scheduled for abortion, provided

the mother consents and the research is properly reviewed. She would not pro-

hibit experimentation which keeps a nonviable fetus alive for a period of time

or which hastens its death.

Joseph Fletcher, D.D.

"Rightness and wrongness are judged according to results, not according to

absolute prohibitions or requirements." This statement provides a key to under-

standing the position taken by Dr. Fletcher regarding the ethics of research on

the fetus. The result which justifies such research is the safety of people,

especially children, from genetic and congenital disorders, uterine infections

and a host of other maladies.

Dr. Fletcher states that the core question is whether the fetus is a per-

son. He contends that although the fetus is a potential person, it does not

become an actual person, ethically and legally, until it is born alive and lives

entirely outside the mother's body with an independent cardiovascular system.

Until the fetus becomes an "actual person" it is an "object," a nonpersonal

organism which has value only insofar as it is wanted by its progenitors. It

is not entitled to protection as a human subject whether viable or not until it

becomes a live-born baby.

Dr. Fletcher states that the following categories of research on the fetus

may be justified, depending upon the clinical situation and the design: (1) use

of a dead fetus ex utero with or without maternal consent; (2) use of a live

fetus ex utero, nonviable or viable, if survival is not wanted and there is

maternal consent; (3) use of a live fetus in utero if survival is not wanted

and there is maternal consent; and (4) use of a live fetus in utero, even if

survival is intended, if there is no substantial risk to the fetus and if there

is maternal and paternal-spouse consent.

32

Finally, Dr. Fletcher concludes that regulations by the Executive Branch

and legislation by Congress (even though temporary) restricting research on the

fetus are unethical if the ethics they are based upon are not fully and frankly

disclosed.

Marc Lappé, Ph.D.

Dr. Lappé's essay is developed from a "natural law" perspective. It

defends five principles pertaining to research on the fetus and makes five

policy recommendations to the Commission.

(1) The wanted fetus has a right to protection in utero. This prin-

ciple is based on its unique vulnerability to environmental insult which might

interfere with the fulfillment of its genetic potential.

(2) Principle (1) is not altered by societal acceptance of abortion.

The Supreme Court has allowed a woman to decide that a fetus will no longer

receive her protection; it does not follow that others in society are similarly

authorized. Further, living fetuses ex utero have claims on our duties to afford

them protection from experimentation by virtue of our basic medical tenets to

preserve life. The Supreme Court offered no guidance on how to treat the fetus

once out of the womb.

(3) The conditions under which society respects the fetus' right to

protection are compromised by the decision and actions taken in the course of

an abortion. Moral concern for the fetus dictates a choice of procedures which

subject the woman to minimal morbidity risks while expeditiously expelling the

fetus and rendering it incapable of survival.

(4) The costs of research on the fetus should be balanced by resul-

tant goods. Society should make efforts to endow the abortion process with

values it would not otherwise have had. Abortion-related research is therefore

justified if and only if it is intended to aid other fetuses.

(5) The definition of fetal death and the application of the defini-

tion must be made independently from any possible future use of the fetus in

experimentation.

33

Dr. Lappé notes that the problem of consent gives us most difficulty in

that even if the fetus were accorded full rights of personhood, it would not do

to delegate the parent as proxy since (in the case of abortion) the parent can-

not be said to have the interests of the fetus at heart. He offers no solution

to the problem, however, except to observe that were the fetus regarded as worthy

of all the rights of personhood, we would not sanction nontherapeutic research

at all.

Dr. Lappé recommends that the Commission (1) affirm its commitment to

protect fetuses in utero; (2) provide a statement of concern for abortion-related

abuse or neglect, including maternal exposure to harmful agents and insensitive

or unethical choice of abortifacients; (3) limit research on the fetus in utero

which is to be a subject of abortion to cases where no risk to the fetus is

involved and the purpose of the research is to aid fetuses as a class; (4) restrict

basic nonviable fetal research intended to benefit society generally to dead

fetuses; and (5) require that fetal death be ascertained by criteria which sepa-

rate the purposes of experimentation from the choice of abortion method and from

the methodology used to ascertain that death has occurred.

Richard A. McCormick, S.J.

Dr. McCormick defends a moral position concerning research on the fetus

and distinguishes it from an acceptable public policy concerning such research.

Public policy is to be determined, not only by morality, but by feasibility as

well. The feasibility test is particularly difficult in a society characterized

by moral pluralism and cultural pragmatism.

Dr. McCormick holds that parents may give proxy or vicarious consent for

a child to participate in nontherapeutic experimentation where there is "no

discernible risk or undue discomfort." Proxy consent is morally legitimate

insofar as it is a reasonable construction of what the child ought to choose if

it were able. This position is rooted in the premise that all humans, including

children, have an obligation in social justice to contribute to the benefit of

the human community. The same obligation can be extended to the fetus. Research

on the fetus is morally permissible if maternal proxy consent is obtained, abortion

is not contemplated, the risk or discomfort to the fetus is not discernible, and

the results of the experiment cannot be obtained in any other way. Because

34

Dr. McCormick judges most abortions to be immoral, experimental procedures prior

to, during, and after abortion (except in the rare instances of legitimate abor-

tion) are morally objectionable because they cooperate with and profit from an

immoral system. While Dr. McCormick regards such cooperation as morally objec-

tionable, he believes that his moral position cannot be fully adopted as public

policy, since it cannot pass the feasibility test in a society which allows large-

scale abortions.

Dr. McCormick recommends that the measure of proxy consent regarded as

valid for subjects of research who are children is suitable to determine accept-

able research on the fetus. He makes the following policy proposals which

acknowledge both the moral pluralism and the cultural pragmatism characteristic

of American society: (1) the research must be necessary; (2) the researcher

bears the onus of showing the necessity; (3) there must be no discernible risk

for the fetus or the mother or, if the fetus is dying, there must be no added

pain or discomfort; (4) the researcher bears the onus of showing that there is

no discernible risk; (5) these policy demands must be secured by adequate review

and prior approval of all research on the fetus.

Paul Ramsey, Ph.D.

Dr. Ramsey seeks to distinguish between fetal life and fetal viability.

Life, he suggests, should be defined for the fetus according to the presence or

absence of vital signs which define life and death in other individuals. Viabil-

ity should not be confused with life, for a fetus may be living yet nonviable.

This new human research subject, one which is neither dead nor viable, is the

subject of Dr. Ramsey's essay. He is not willing to say it may be entered into

research protocols, but he does say that care should be taken not to enter a

viable infant by mistake. To this end he recommends that viability be defined

for research purposes on the safe side of possibly viable birth weight, crown-

rump length or gestational age. He makes the following proposals to the Com-

mission:

(1) The Peel Report prohibits procedures carried out with the delib-

erate intent of ascertaining the harm they might do to the fetus. Such a pro-

hibition should be included in the American policy as well. "DO not harm"

35

encompases "intend no harm." This principle embraces the intention of the

physician and not merely "codes of action."

(2) The subjective rule (Peel) must be supplemented by an objective

limitation of risks by categorically prohibiting research in anticipation of

abortion if that research entails known or uncertain risks.

(3) Respect for the dignity of human life must not be compromised

whatever the age, circumstances, or expectation of life of the individual. The

recent Supreme Court decision on abortion did not nullify the obligation to pro-

tect the developing fetus from harm, even if that harm is less than abortion.

(4) Vital functions of an individual abortus should not be artifi-

cially maintained except where the purpose of the activity is to develop new

methods for enabling that abortus to survive to the point of viability.

(5) Ethical standards applicable to research on the fetus are the

same as would be subscribed to in proposed research on the unconscious, on the

dying (in the case of spontaneous abortion), on the (perhaps justly) condemned

(in cases of induced abortion), or in experimentation with children.

For the most part, this means that the use of these subjects in nonthera-

peutic research is an abuse, for one ought not to "presume" or "construe" consent

for acts of charity. Dr. Ramsey agrees with Dr. McCormick that "one stops and

should stop precisely at the point where 'construed' consent does indeed involve

self-sacrifice or works of mercy. The dividing line is reached when experiments

involve discernible risk, undue discomfort, or inconvenience."

Seymour Siegel, D.H.L.

Dr. Siegel makes the following points:

(1) A bias for life is the foundation of the Judeo-Christian world-

view and it undergirds medical research. It may be affirmed outside the Judeo-

Christian tradition. The bias for life requires individuals to strive to sustain

life where it exists, not to terminate or harm life, and in cases of doubt to

be on the side of life. A present individual takes precedence over a possible

future individual. The bias for life is to be exercised whatever the status of

the life before us and whatever the life expectation may be.

36

(2) The indeterminancy of the future requires that utmost caution

should be employed in all decisions relating to research on the fetus, since

neither the medical nor the social effects of such research can be predicted

with certainty.

(3) The fetus is not the same as an infant since it has no indepen-

dent life system and is tied to the mother.

(4) A fetus has real but limited rights, derived from its potential

human life. The fetus' right to life is mitigated when the fetus threatens

someone else's life; however, unless such a threat is present, the fetus'

potential humanity requires that we protect and revere its life.

(5) The fetus in utero may be the subject of research that (a) helps

the mother, (b) is harmless to the fetus, or (c) is designed to help the fetus.

Dr. Siegel endorses the Peel Commission dictum that no procedures may be carried

out to see what harm they might do the fetus.

(6) The fetus ex utero has more rights than the fetus in utero. Pro-

longation or early termination of the nonviable fetus should be prohibited.

(7) Criteria for death of the fetus should be the same as for other

individuals.

(8) Consent of the mother or guardian is ordinarily sufficient, but

parental consent, when an abortion is contemplated, is dubious. For such cases,

consent should be supplemented by a special board. There must be strict separa-

tion of attending physician and researcher.

(9) Proposed guidelines: (a) fetal research should be limited to

cases which present no harm or offer assistance to the life system of the sub-

jects; (b) no procedures should be permitted which are likely to harm the

fetus--before, during, or after abortion; (c) a fetus ex utero and alive should

not be subject to research unless it is intended to enhance the life of that

fetus or unless the research involves no risk to the subject; and (d) criteria

for determining death of the fetus should be the same as for other human indivi-

duals.

37

LeRoy Walters, Ph.D.

Dr. Walters surveys various ways of categorizing research on the fetus:

(1) according to the condition of the fetus, (2) according to the chronological

age of the fetus, and (3) according to the formal object of the research.

He concludes that research on the fetus is not one but many things, and

he focuses on nontherapeutic research on the fetus because it seems to raise

serious public policy questions, and on research before, during and after

induced abortion since that is a primary concern of the Commission's authorizing

legislation. Four possible positions can be developed with respect to such

research. Dr. Walters defends the position that nontherapeutic research on the

fetus should be permitted only to the extent that such research is permitted on

children or on fetuses which will be carried to term.

The essay endorses McCormick's thesis that parents may properly consent

to a child's participation in nontherapeutic research which the child should

be willing to take part in if the child were able to consent. This position

is extended to cover the prenatal period as well. Because of difficulties

associated with consent in cases where an abortion decision has been made, non-

therapeutic research procedures should be permissible in the case of fetuses

before or after abortion to the extent that they are permissible in the case of

fetuses which will be brought to term. This position supposes that there is

substantial continuity between previable and viable fetal life and postnatal life.

Although public policy making includes an ethical component, it also

includes other factors, such as continuity with generally accepted societal

principles, accommodation of a variety of belief systems and interests, and

clearly understandable formulation. Three public policy propositions are

recommended, all of which are based upon a policy of equality of treatment for

all categories of human subjects: (1) nontherapeutic research on children

should be permitted, if such research involves no risk or only minimal risk to

subjects; (2) nontherapeutic research on fetuses which will be carried to term

should be permitted, if such research involves no risk or minimal risk to the

subjects; (3) nontherapeutic research procedures which are permitted in the

case of fetuses which will be carried to term should also be permitted in the

case of (a) live fetuses which will be aborted and (b) live fetuses which have

been aborted.

38

Richard Wasserstrom, Ph.D.

Dr. Wasserstrom identifies four views concerning the status of the human

fetus. He endorses the view that the fetus is in a unique moral category,

closest to that of a newborn infant. The fetus has great value because of its

potential to become a fully developed human being. It follows that abortion is

morally worrisome because it involves destruction of an entity that possesses

the potential to be and to produce things of the highest value. It also follows

that if abortion has already taken place and the fetus is nonviable, then

research in no way affects the fetus' ability to realize any of its potential.

Dr. Wasserstrom states that the resolution of the problem of consent for

research on the fetus depends entirely on how one views the status of the fetus.

That is, if one views the fetus as tissue, then consent on behalf of the fetus

is meaningless. If one views the fetus as a child, then proxy consent is

necessary. Dr. Wasserstrom believes, however, that even if the fetus is con-

sidered to be only tissue, consent should be obtained from the parents out of

respect for their sensitivities.

Because abortion is a morally worrisome act, the decision to have an

abortion should be kept easily revocable until the time of its performance. For

this reason, Dr. Wasserstrom recommends that no research on the fetus in utero

should be permitted if it involves a substantial risk of injury to the fetus.

Dr. Wasserstrom concludes that research on the nonviable fetus ex utero

is permissible provided that: (1) the mother (if unmarried) or both parents

consent before the abortion; (2) a review body has determined that the research

may yield important information not otherwise obtainable; (3) the medical

counselors of the pregnant woman have in no way been affiliated with the

experimentation; and (4) the fetus is not possibly viable.

(An analysis of the papers summarized above was prepared for the Com-

mission by Stephen Toulmin, Ph.D. This analysis is set forth in its entirety

in the Appendix.)

39

VI.

VIEWS PRESENTED AT PUBLIC HEARINGS

Public hearings were held by the Commission to provide interested persons

with an opportunity to present their views on research on the fetus. Testimony

was given by scientists, physicians, representatives of various organizations,

concerned private citizens, lawyers and public officials. They presented a broad

range of views that received careful consideration at the hearings and in the

subsequent deliberations of the Commission. Brief summaries of the presentations

follow.

1. C. D. Christian, M.D. (American College of Obstetricians and

Gynecologists). Dr. Christian presented to the Commission a set of guidelines

for the conduct of research on the pregnant woman and fetus, as prepared by the

Committee on Bioethics of the College. The guidelines include recommendations

that animal models be fully explored before human research is initiated, that

clinical management of the patient should not be altered by research objectives,

that research which would knowingly harm the fetus is not appropriate even in

anticipation of abortion, that a fetus of doubtful viability should be treated

as a viable infant, and that prolonging or shortening the life of the nonviable

fetus only for research purposes is not appropriate.

2. Robert G. Marshall (Special Assistant for Congressional Affairs, U.S.

Coalition for Life). Mr. Marshall opposed any research that is not directed at

preserving the life or restoring the health of the immediate patient. In addi-

tion, he suggested adoption of the Golden Rule as a criterion for experimentation;

a prohibition on the participation of the medically needy as subjects of research,

except in circumstances of immediate danger to life; and a requirement that pros-

pective participants be required to write out their understanding of the purpose

of an experiment prior to being accepted as subjects. (During questioning, Mr.

Marshall said that he would not object to observational procedures including,

for example, fetoscopy.)

41

3. Thomas K. Oliver, Jr., M.D. (Association of American Medical Colleges).

Dr. Oliver cited improvement in statistics of infant mortality and morbidity,

which may be attributed directly to research on the fetus and newborn infant.

He described the research leading to improved care of Rh disease and respiratory

distress syndrome, which could have been conducted only on the human fetus and

newborn, as specific examples of advances resulting from research on the fetus.

He urged the creation of an Ethical Advisory Board to review those research pro-

posals which raise ethical questions, rather than the imposition of guidelines

that would not be responsive to changing circumstances.

4. Judith Mears (Reproductive Freedom Project, American Civil Liberties

Union). Ms. Mears urged that the Commission not draft protections for the fetus

that would undermine the Supreme Court's rulings in Doe v . Bolton and Roe v . Wade

regarding a woman's rights with respect to abortion. In addition, she urged the

support of research to improve the safety of abortion procedures. (Ms. Mears

agreed, during questioning, that the Roe and Doe decisions do not speak to the

issue of experimentation and would not, therefore, render regulation of such

research unconstitutional so long as a woman's access to abortion and other

health services is not abridged.)

5. David G. Nathan, M.D. (Professor of Pediatrics, Harvard Medical School).

Dr. Nathan focused his discussion on fetoscopy. He described this experimental

technique for obtaining a sample of fetal blood to enable prenatal detection of

disorders such as sickle cell disease and thalassemia, the reasons for conducting

initial trials in women about to undergo abortion, and the evolution of the tech-

nique to the point where it has had successful clinical application. Dr. Nathan

stressed the importance of studies that can be conducted simultaneously with the

abortion procedure and consequently avoid any possibility of a change of mind

about abortion after the research has begun.

6. Audrey McMahon (mother of two developmentally disabled children).

Ms. McMahon stressed the need for research into the causes and treatment of

developmental disabilities, and urged that such research not be curtailed.

42

7. Robert Greenberg, M.D. (Society for Pediatric Research and the

American Pediatric Society). Dr. Greenberg presented statistics on the high

rates of infant mortality and abnormal fetal development as indicators that the

current health status of the fetus is poor. Dr. Greenberg stated that genuine

concern for the fetus requires marked improvement of the health care available

to the developing human during intrauterine life. Such improvements in health

care require acquisition of further understanding through increased research.

8. Sumner Yaffe, M.D. (American Academy of Pediatrics). Dr. Yaffe cited

numerous advances in fetal therapeutics resulting from research on the fetus and

emphasized the acute need for more extensive research in fetal clinical pharma-

cology. He presented the Academy's code of ethics for research involving the

fetus and fetal material. The code states that research intended to benefit the

mother or fetus in utero may be conducted with informed consent; that research

on the viable delivered fetus (premature infant) may be carried out as long as

nothing is done that is inconsistent with treatment necessary to promote the

life of the infant; and that research on the nonviable fetus before or after

abortion should be permitted, providing appropriate animal studies have been

completed, parental consent is obtained, the researchers have no part in deciding

timing or procedures for terminating the pregnancy or in determining viability,

the research has been approved by an Institutional Review Board which is satis-

fied that the information cannot be obtained in any other way, experiments are

not done in the delivery room, there is no monetary exchange for fetal material,

and full records are kept.

9. Lois Schiffer (Women's Equity Action League, Women's Legal Defense

Fund, Human Rights for Women). Ms. Schiffer cautioned against developing a pol-

icy that would abrogate constitutionally protected interests, such as the pre-

eminence of a pregnant woman's right to health care. She underscored the need

for continuing research in order to provide pregnant women with optimum medical

advice and treatment (including improved abortion techniques). She suggested,

additionally, that a requirement of paternal or spousal consent in conjunction

with research on the fetus would contravene the holdings in the Roe and Doe deci-

sions and that such consent serves no legitimate purpose if no child will be born.

43

Finally, she urged the adequate representation of women on ethical review com-

mittees that will be applying policy to specific cases.

10. Kay Jacobs Katz (National Capital Tay-Sachs Foundation). Ms. Katz

described the illness and death of her daughter, a victim of Tay-Sachs disease,

and emphasized that only because of the availability of prenatal diagnosis did

she have the courage to risk a further pregnancy that has resulted in the birth

of a normal child. She urged the Commission not to restrict research that might

develop procedures for prenatal diagnosis of other genetic diseases, nor to cur-

tail research that might lead to the development of effective therapy for inborn

errors of metabolism.

11. Arthur M. Silverstein, Ph.D. (American Society for Experimental

Pathology). Dr. Silverstein pointed out the limitations of animals as models for

the human fetus in experimentation. He cited the numerous uses of cells and tis-

sues from the dead fetus in biomedical science, and urged that scientists not be

deprived of the opportunity to study such tissues. He urged continued availabil-

ity of fresh fetal materials for study and for use in transplantation. He con-

cluded by asking the Commission to recognize that society owes to the developing

fetus an acknowledgement of its special problems and a determination to attempt

to solve these problems and do medical justice to the fetus through research.

12. Msgr. James T. McHugh (U.S. Catholic Conference). Msgr. McHugh

stated that the fetus is a human being from the earliest stages of development,

and that the ethical norms governing research on the fetus derive from those

governing research on all human subjects, especially infants and children. Pre-

abortion research is inconsistent with human dignity and is therefore unacceptable.

Consent by the mother to such research is a mockery, he said, inasmuch as she has

already decided to extinguish the life of the fetus; further, such research would

eliminate any possibility of a mother's change of mind concerning abortion.

He urged Federal regulations of research on the fetus to permit only pro-

jects involving, for example, amniocentesis, fetoscopy, tissue culture, or proce-

dures that would entail no risk to the fetus, and to limit those to circumstances

in which their application would serve the purpose of protecting maternal health

44

and assuring safe delivery of the fetus. He urged that animal models be used

to the extent possible, even if this would be more expensive and demanding. He

stated that the Government should permit research on the fetus only for the pur-

pose of enhancing the survival or well-being of the fetus involved, and only if

it can be conducted in a manner that will respect the rights and dignity of the

fetus.

13. Jo Anne Brasel, M.D. (Endocrine Society). Dr. Brasel cited examples

of contributions of fetal endocrinologic research to fetal welfare and survival.

Continuation of research on the fetus was urged to permit study of such problems

as hormonal deficiency states and care of the fetus of the diabetic mother. She

expressed the full support of the Society for efforts to see that ethical consid-

erations are met in the conduct of human research, but asserted that the welfare

of future mothers and infants would not be served by wholesale interdiction of

research.

14. Nancy Raymond, R.N. (Public Relations Director, Maryland Action for

Human Life). Ms. Raymond urged that the fetus be treated with fairness and

dignity, whether or not an abortion is anticipated or has been conducted. She

advocated a prohibition of research on the fetus, but would make the following

exceptions from such a prohibition: remedial procedures; procedures to study

the fetus within the womb, if they do not substantially jeopardize the fetus and

it is not a candidate for planned abortion; diagnostic procedures that do not

substantially jeopardize the fetus, even if it is a candidate for planned abor-

tion; and diagnostic procedures that are judged to be in the best interest of

the particular fetus and will provide the mother with information about her fetus,

even if an abortion is contemplated. She suggested that a panel of medical and

nonmedical persons be created to advise scientists on the acceptability of

research on the fetus.

15. Sean O'Reilly, M.D. (Professor of Neurology at George Washington

University). Dr. O'Reilly's testimony (read in his absence) urged protection

of the fetus from experimentation without its informed consent. He stated that

the fetus obviously cannot give consent, and that parents can consent only to

45

therapeutic research on the fetus. He argued that parents forfeit any right to

consent to any other research on the fetus once they have elected to abort it.

16. Chris Mooney (President, Pregnancy Aid Centers, Inc.) Ms. Mooney

viewed abortion as the worst solution to the problem of unwanted pregnancy,

preferring to improve methods and availability of counseling and contraception.

She expressed the fear that research on the fetus before and after abortion will

further entrench our dependence on this pseudo-solution, by persuading women to

abort in order to contribute to the cause of science. If science becomes depen-

dent on abortion for research subjects, scientists and society will be even less

inclined to develop viable alternatives to abortion. She urged that no money be

offered for the use of an aborted fetus in research. (During questioning, Ms.

Mooney said she has no knowledge of cases in which research did, in fact, operate

as an inducement to abortion, and agreed that regulations could be devised to

avoid that possibility.)

17. Walter L. Herrmann, M.D. (Society for Gynecologic Investigation).

Dr. Herrmann pointed out that the interrelation of mother and fetus in utero

requires that they both be considered in research involving either of them. He

observed that the attitude of confidence rather than fear of the modern woman

contemplating pregnancy is due to improved pregnancy care resulting from maternal

and fetal research. Many unanswered questions remain, however, which demand

continuation of such research. He urged that, in developing regulations for

research on the fetus, the abortion issue be kept separate and emphasis be placed

on the pregnant women as the subject to be protected, so as not to infringe upon

her rights or deprive her of the benefits of scientific discovery.

18. Mary O'Donnell (Nursing student; member, National Youth Pro-Life

Coalition). Ms. O'Donnell argued that fetal life is human life deserving of our

respect and protection. She would permit diagnostic procedures when undertaken

to promote well-being or survival, and all life-preserving procedures. She would

find drug research in anticipation of abortion unacceptable because it deprives

a woman of the opportunity to change her mind and violates basic moral values.

46

19. Leroy A. Jackson, M.D. (Obstetrician in private practice, Washington,

D.C.). Dr. Jackson cited procedures derived from research on the fetus that have

improved his ability as a physician to provide medical care to his patients. He

focused his testimony on the need to assure that consent from the mother for

research on the fetus is truly informed consent, and that minorities and other

groups do not bear a disproportionate share of the research burden. To these

ends, he urged that research review committees contain members racially repre-

sentative of and capable of communicating adequately with individuals on whom

the research is conducted, that consent form wording be reviewed in detail, and

that non-Government research agencies follow Government guidelines.

20. Karen Mulhauser (National Abortion Rights Action League). Ms. Mul-

hauser urged that the Commission recommend no limitations on research on the

nonviable fetus in utero, provided informed consent is received from the preg-

nant woman. She also opposed any limitation of research to develop improved

and safer abortion techniques.

21. Ernest L. Hopkins, M.D. (Professor of Obstetrics and Gynecology,

Howard University). Dr. Hopkins cited statistics indicating that black infants

and mothers have markedly higher morbidity and mortality in childbirth and the

first year of life than do whites, and thus have a significant stake in research

directed toward pregnancy and infancy. It is essential that research be con-

ducted, he stated, as well as mandatory that the rights of the subject be pro-

tected. He advised the Commission that a mother often arrives at a decision to

terminate pregnancy because she cannot support her present family. These are

honorable women with wisdom, he said. They are very emotionally involved with

the pregnancy, but they know the birth of a baby would be catastrophic. They decide, reluctantly, to have an abortion because they see no alternative.

22. J. V. Klavins, Ph.D. (Professor of Pathology, State University of

New York at Stony Brook). Dr. Klavins suggested that research on the fetus could

be conducted with consent of the mother (and father when available). Since abor-

tion is legal, he argued, research that causes no harm or suffering to the fetus-

to-be-aborted is certainly acceptable. He stated that research on the human

47

fetus is no more likely to be dehumanizing than artificial insemination has

been, that "do no harm" be used as the guiding principle in research on the

fetus, and that society not be allowed to interfere with the parents' right to

make decisions concerning the best interest of their offspring.

23. Myron Winick, M.D. (American Institute of Nutrition and the American

Society for Clinical Nutrition). Dr. Winick reviewed nutrition problems relevant

to the fetus and cited research needed to approach solutions to such problems.

For example, knowledge is needed of the way the human fetus gets and uses essen-

tial nutrients in utero. Acquisition of this knowledge may require nonbeneficial

research, he stated. The aim of the research, he pointed out, is to improve

fetal growth and the quality of life, and, when a malnourished fetus is identi-

fied, to assist the fetus, not to terminate the pregnancy.

24. Aubrey Milunsky, M.D. (Assistant Professor of Pediatrics, Harvard

Medical School). Dr. Milunsky presented written testimony focusing on prenatal

diagnosis of genetic disease by amniocentesis. He pointed out that research on

the fetus was essential to developing amniocentesis, which is now an accepted

clinical procedure. The research aspects of prenatal diagnosis now involve

extending diagnostic possibilities to other diseases and developing methods of

prenatal treatment of an affected fetus as an alternative to abortion. He argued

that to halt such research now would prohibit extending to other populations

(such as those affected by sickle cell disease) the option of prenatal diagnosis,

and also would prohibit the possible development of treatments for the diagnosed

diseases.

25. Louis Hellman, M.D. (Deputy Assistant Secretary for Population

Affairs, DHEW). Dr. Hellman reviewed the activities of his office in supporting

research and providing services in family planning, noting that the objectives

directly affected the health of mothers and infants. Enabling women to have

fewer children implies that those born should have optimum chances for survival

and good health. Thus, the Office of Population Affairs has an interest in all

aspects of maternal and fetal research directed at reducing mortality and mor-

bidity. In the conduct of such research, Dr. Hellman stated, obtaining properly

48

informed consent and review of the research by a committee of peers do not con-

stitute significant barriers. He advocated conducting such reviews locally

rather than in Washington. He expressed a personal distaste for nonbeneficial

research on the aborted fetus, for which an outright prohibition might be con-

sidered, but cautioned that such a course would be unlikely to stop the search

for new knowledge, perhaps in another country or in another generation. He con-

cluded that knowledge cannot be sequestered nor the course of its attainment

blocked, and he suggested that the wiser direction would be adequate regulation

of research on the fetus rather than outright prohibition.

26. Norman Kretchmer, M.D. (Director, National Institute of Child Health

and Human Development, National Institutes of Health). Dr. Kretchmer summarized

the policies and procedures presently in effect at NIH for the protection of human

subjects studied in research activities. Proposals involving extramural research

(which is conducted at institutions other than NIH) undergo a three-stage process

of review, including: (1) review by the institution proposing the research,

(2) review by scientific peers acting as consultants to NIH, and (3) review by

the National Advisory Councils of the Institutes supporting the projects.

The first stage is performed by an Institutional Review Board (IRB), a

panel consisting of members with diverse backgrounds and drawn from various dis-

ciplines. It is the responsibility of the IRB to review the proposal for scien-

tific merit, community acceptability, the balance of risks and benefits, and any

other factors that might bear upon the protection of the rights and welfare of

the subjects.

The second stage of review is conducted by scientific peers, to evaluate

the soundness of the research design, the relevant professional experience of

the investigator, adequacy of facilities, scientific importance of the research,

and the like. In addition, the reviewing body may consider the investigator's

evaluation of risks and benefits, as well as any procedures suggested to protect

the subjects against possible risks.

The final stage of review is conducted by a National Advisory Council,

a panel composed of two-thirds scientists and one-third nonscientists. Their

responsibility is to recommend policy for the Institute and to advise the

49

Director, NIH (or, in some cases, the Secretary, DHEW) concerning funding of

research proposals, giving consideration to the protection of the rights of human

subjects, among other things.

Research conducted within NIH (intramural research) undergoes review by

the branch chief and clinical director of the Institute conducting the research.

It may also be subject to review and approval by the Clinical Research Committee

and the Medical Board of the Clinical Center. The Medical Board includes in its

membership clinicians, scientists and laymen. All studies involving normal vol-

unteers must be submitted to the Medical Board. Studies which involve potential

benefits to patients who have been admitted to the Clinical Center generally are

reviewed by clinical associates, attending physicians and the chief of the branch

involved. When such studies represent a significant deviation from accepted prac-

tice or are associated with unusual hazards, however, they must be reviewed by

the Clinical Research Committee.

For fiscal year 1974, NIH has identified about one hundred projects (with

a total support of $3.5 million) which involved research on the fetus. These

included monitoring of labor, fetal response to growth promoting substances,

development of a "fetal risk index," and others. Under the ban imposed by

P.L. 93-348, research on the living human fetus, before or after induced abor-

tion, is not supported by NIH unless such research is done with the intention

of assisting the survival of the fetus.

27. John Jennings, M.D. (Associate Commissioner, Food and Drug Adminis-

tration).* Dr. Jennings testified that FDA has legislative authority to ensure

that research submitted to the agency by industry to show the safety and effec-

tiveness of a drug is conducted under conditions that will protect subjects. In

this regard, FDA believes it should act in accord, insofar as feasible, with DHEW

guidelines for protection of human subjects in research conducted or supported

by the Department.

*Dr. Jennings was accompanied by Dr. Frances Kelsey, Dr. Carl Leventhal and Mr. William Vodra.

50

Most drugs currently marketed bear a warning on that label that they

have not been tested for safety in pregnant women. Nevertheless, Dr. Jennings

stated, such drugs, with potentially harmful effects on the fetus, are being

used by pregnant women and by woman of childbearing age, in spite of the label

disclaimers. Therefore, the American Academy of Pediatrics has recommended to

FDA that all marketed drugs be evaluated regarding their potential for producing

adverse effects in the fetus.

Dr. Jennings expressed confidence that although difficult ethical problems

are raised by research on the fetus, the Commission would be able to develop

flexible guidelines that would safeguard both consumers and subjects.

In response to questions, representatives from FDA explained that no mar-

keting of a drug is permitted until tests on animal teratology and reproduction

have been completed. These tests include: (1) studies of normal and reproduc-

tive performance from the beginning of pregnancy through delivery, following

administration of the drug to both males and females, (2) studies of teratology,

following administration of the drug during pregnancy at the time of organ devel-

opment, and (3) tests following administration of the drug from the end of preg-

nancy through lactation. FDA requests additional studies in primates if first

studies indicate a need for further investigation.

51

VII.

FETAL VIABILITY AND DEATH

The definitions of fetal viability and death present important issues in

the conduct of research on the fetus. Accordingly, the Commission contracted

for two studies in this area: the first, a medical study to define fetal

viability and death based on present capabilities of medical technology; the

second, an analysis of ethical and philosophical as well as scientific consid-

erations in defining fetal viability and death.

The first study was conducted under contract with Columbia University,

Richard Behrman, M.D., Principal Investigator. It included (1) a survey of the

changes over the last 10 years in survival rates of premature infants and the

advances in technology that have contributed to improved survival; (2) an

assessment of the present state of medical technology designed to sustain pre-

mature infants; and (3) based on the foregoing, a recommendation for guidelines

for use by physicians in determining whether a fetus, delivered spontaneously

or by induced abortion, is viable, nonviable or dead. Consultation with

representatives of professional societies in pediatrics and obstetrics, surveys

of selected newborn intensive care units in the United States and Canada,

charge.

statistical surveys and literature reviews were employed in carrying out this

Assessment of changes in survival of premature infants relied primarily

on data from New York City and from geographically dispersed infant intensive

care units, as no national or international data broken down by weight group

under 2500 grams were available. New York data showed a 4.5 percent increase

in survival rate (26 percent reduction in mortality) of all infants under

2500 grams for the period covering the years 1962 to 1971. The improvement was

primarily in the lower weight groups: 68 percent increase in survival rate

under 1000 grams, 20 percent increase from 1001 to 1500 grams, and 6 percent

from 1501 to 2000 grams. Infants cared for in intensive care units showed an

even greater improvement in survival.

53

Many innovations in caring for the fetus in utero and the delivered pre-

mature infant were introduced in the last decade. The large number of these

innovations, and their introduction at different times in different centers,

generally made it impossible to establish a direct correlation between a given

technologic innovation and a change in infant survival. One exception, where

such a correlation may be made, is the effect on survival of monitoring fetal

heart rate and acid-base balance during labor. At Los Angeles County USC

Medical Center, monitoring was introduced as a routine procedure for high risk

obstetrical patients in 1970; low risk patients were unmonitored. Between 1970

and 1973, the intrapartum death rate of infants weighing more than 1500 grams

decreased 64 percent, and the fetal death rate became lower for the monitored

high risk women than in the unmonitored low risk women. Comparable results

were obtained in New York City at Columbia Presbyterian Medical Center, where

over 90 percent of the monitoring was done on high risk ward patients, primar-

ily black, poor or Spanish-speaking; the low risk private patients were unmoni-

tored. Following introduction of monitoring, the high risk monitored patients

had 10 percent fewer fetal deaths, 14 percent fewer perinatal deaths, and

37 percent fewer intrapartum fetal deaths than the unmonitored low risk private

patients.

Overall improvement in premature survival may be traced more generally

to the gradual adoption of other innovations. For example, the improved rates

during the years 1967 through 1969 may be related to advances first introduced

during the years 1964 through 1966, which included amniocentesis for intrauterine

diagnosis of infants severely affected with erythroblastosis; fetal transfusion

in utero; reorganization of premature nurseries into intensive care centers;

extensive monitoring of gases and other substances in blood, and of vital signs,

with more aggressive attention to correction of abnormal values; hand ventilation

with ambu bags; regulation of the thermal environment; and greater density of

nursing personnel. Increases in survival in the period 1970 to 1973 may be cor-

related with a constellation of advances in the years 1968 through 1970. These

included extensive study of amniotic fluid in managing high risk pregnancies;

fetal heart rate and uterine pressure monitoring during labor; improved infant

transport systems and referral to intensive care units; major advances in design

and techniques for use of infant respirators; total intravenous alimentation;

54

and use of phototherapy for jaundice. Numerous other innovations have been

introduced, but these are the major advances that have come into widespread use.

Impact of these changes on survival is reflected in data from University

College Hospital in London, where survival rate of infants 1001 to 1500 grams

was a steady 45 to 50 percent during the 1950's and early 1960's. During the

period 1966 to 1970, the survival rate increased to 70 percent. Equally sig-

nificant is an indication of decreased morbidity. During the 1950's and 1960's,

the handicap rate for infants weighing less than 1500 grams at birth ranged

from 33 percent to 60 percent. A recent study evaluating the outcome of such

infants born from 1966 to 1970 indicated that 90.5 percent had no detectable

handicap.

Despite these advances in the technology of caring for premature infants,

there remain limits beyond which the best care cannot result in survival. To

ascertain the present limits, surveys were conducted of vital statistics of the

United States (including individual states) and Quebec, the medical literature,

and 27 major centers with obstetric services and special intensive care units

for premature infants. These centers represent the optimal care that present

medical technology can provide. Despite differences in data base from various

sources, two facts emerged clearly: probability of survival of infants weighing

less than 750 grams was extremely small, and no cases were found from any docu-

mentable source of any infant surviving with a birth weight below 600 grams at

a gestational age of 24 weeks or less. Some rare cases were documented of

infants surviving with birth weights below 600 grams, but in each instance, the

gestational age exceeded 24 weeks, and the cases thus represented more mature

infants who for various reasons were small-for-dates. Other rare cases were

documented of infants born before 25 weeks gestational age who survived, but in

each instance birth weight exceeded 600 grams. Thus, on an empirical, basis the

current limits of viability are clear: there is no unambiguous documentation

that an infant born weighing less than 601 grams at a gestational age of 24 weeks

or less has ever survived.

The concept of viability implies a prediction as to whether a delivered

fetus is capable of survival. A prematurely delivered fetus is viable when a

minimal number of independently sustained, basic, integrative physiologic func-

tions are present. The sum of these functions must support the inference that

55

the fetus is able to increase in tissue mass (growth) and increase the number,

complexity and coordination of basic physiologic functions (development) as a

self-sustaining organism. This development must be independent of any connection

with the mother and supported only by generally accepted medical treatments. If

these coordinated functions are not present, the fetus is nonviable. This may

be the case even though some signs of life are apparent.

The following functions, taken together, constitute the minimal number of

basic integrative physiologic functions to support an inference of viability:

(1) Perfusion of tissues with adequate oxygen and prevention of increasing

accumulation of carbon dioxide and/or lactic and other organic acids. This

function consists of the following components:

(a) inflation of the lungs with oxygen,

(b) transfer of oxygen across the alveolar membranes into the cir-

culation and elimination of carbon dioxide from the circulation into the expired

gas, and

(c) Cardiac contractions of sufficient strength and regularity to

distribute oxygenated blood to tissues and organs throughout the body, and to

eliminate organic acids from those tissues and organs.

(2) Neurologic regulation of the components of the cardio-respiratory perfusion

function, of the capacity to ingest nutrients, and of spontaneous and reflex

muscle movements.

These functions in the prematurely delivered fetus cannot at present be

assessed separately in a consistent, reliable and exact manner. The absence of

the sum of these functions, however, can be assessed indirectly in a reasonable

and reliable manner by measurement of weight and an estimation of gestational

age. Thus, organisms of less than 601 grams at delivery and gestational age of

24 weeks or less are at present nonviable; signs of life such as a beating heart,

spontaneous respiratory movement, pulsation of the umbilical cord and sponta-

neous movement of voluntary muscles are not adequate in themselves to be used to

determine the existence of basic integrative functions.

A weight of 601 grams or more and gestational age over 24 weeks may indi-

cate that the minimal basic functions necessary for independent growth and

56

development are present. Such a prematurely delivered fetus may be considered

at least possibly viable. At these weights and gestational ages, a sign of life

such as a beating heart, spontaneous respiratory movement, pulsation of the

umbilical cord or spontaneous movement of voluntary muscles indicates possible

viability.

Prediction of extrauterine viability of the fetus while it is still in utero

takes on an additional dimension of complexity. The fetus in utero, in the absence

of clear signs that death has occurred, is always at least potentially viable as

long as it remains in the uterus. However, it cannot be weighed, size assessments

based on uterine size are inaccurate, and estimates of gestational age based on

menstrual history are often inexact. The best medical technology can provide at

present is an index of gestational age based on measurement of head size, using

ultrasound. In the best hands, this technique is accurate within ±1 week at

20-26 weeks. Relating gestational age to fetal weight, and taking into account

the range of error and normal variation, an estimated gestational age of 22 weeks

or less by ultrasound would virtually eliminate the possibility of fetal weight

above 600 grams and actual gestational age greater than 24 weeks. Such an esti-

mate would permit the prediction that if such a fetus were outside the uterus, it

would be nonviable.

Employing present technology, therefore, research on the fetus in utero,

undertaken before an abortion to occur not later than 22 weeks gestational age

as estimated by ultrasound, would not impact on a fetus with a chance for survival

after the abortion. Any reduction of the 22 week limit would provide an additional

safeguard.

Whatever the boundaries are for viability, there is always a chance that a

viable infant may be born after a prediction of nonviability by gestational age.

When this occurs, the premature infant clearly must be cared for in accord with

accepted medical practice. Further, these criteria for viability are based on

current technology, which is subject to change. Accordingly, the criteria should

be reviewed periodically.

Death of the delivered fetus is judged to have occurred when there is a

cessation of the minimal basic integrative physiologic functions which, considered

together, may result in self-sustained extrauterine growth and development. The

57

absence of all of the following signs indicates the cessation of these minimal

basic integrative physiologic functions:

(1) heart beat,

(2) spontaneous respiratory movements,

(3) spontaneous movement of voluntary muscles, and

(4) pulsation of the umbilical cord.

Approaching the same issues of fetal viability and death from the view-

point of a physician-scientist and philosopher, Dr. Leon Kass, in an essay pre-

pared for the Commission, came to conclusions similar to those reached by

Dr. Behrman on criteria for determining death and defining fetal viability

(though Dr. Kass was more conservative on the latter). In clarifying the termi-

nology, Dr. Kass distinguished between the terms "viable" and "nonviable" (which

refer to states of a living fetus) and "alive" and "dead" (which refer to mutually

exclusive conditions of the organism independent of its stage of development).

The terms "viable" and "nonviable" are predictive of future outcome, which is

dependent on the fetal stage of development and relation to the environment.

Thus, the determination of viability is influenced by whether the fetus is inside

or outside the uterus, and by the technology available for sustaining life. A

fetus that is alive inside the uterus is always at least potentially viable; the

same fetus outside the uterus may be viable or nonviable.

As criteria for determining death, Dr. Kass suggested that a fetus be con-

sidered dead if, based on ordinary procedures of medical practice, it has experi-

enced an irreversible cessation of spontaneous circulatory and respiratory func-

tions and an irreversible cessation of spontaneous central nervous functions.

These criteria are evidenced on examination of the fetus by absence of the

following:

(1) spontaneous muscular movement,

(2) response to external stimuli,

(3) elicitable reflexes,

(4) spontaneous respiration, and

(5) spontaneous heart function manifested by heartbeat and pulse.

58

These criteria differ from those suggested by Dr. Behrman only by the addition

of (2) and (3). Dr. Kass advised that the presence of any one of these functions

is a sign that the fetus is alive (again in agreement with Dr. Behrman), and he

further suggested that use of the EEG is unnecessary in making the diagnosis of

death. Finally, he recommended that the fetus in utero be considered alive until

proved dead, and that the fetus being aborted be presumed alive until examination

reveals it to be dead.

A viable fetus was defined by Dr. Kass as one that has reached the stage

of development at which it is able to sustain itself outside the mother's body.

In suggesting criteria for fetal viability based on present technology, Dr. Kass

supported use of essentially the same physiologic criteria as suggested by

Dr. Behrman, but would not rely upon weight or gestational age to indicate the

presence of these integrated functions in the delivered fetus. He suggested

that the delivered fetus should be considered viable in the presence of all five

of the functions listed above (the absence of which is definitive of death). Of

these, respiratory activity is the sine qua non of viability. Following delivery

of the fetus, adequate time should be allowed to assess the presence of life and

determine viability before research involving the fetus can be considered. This

evaluation should be made by the delivering obstetrician, and then only if he is

not himself likely to be engaged in subsequent research involving the fetus.

It is more difficult to determine whether the fetus in utero would be

viable, if delivered, and, due to the possibility of error, Dr. Kass advised

caution. He suggested that viability of the fetus in utero be evaluated

according to gestational age. The fetus in utero is potentially viable before

20 weeks gestational age, but nonviable if removed from the uterus. It should

be considered viable after the age of 28 weeks. Accurate evaluation of the

viability of a fetus in utero between 20 and 28 weeks gestational age is not

possible; such a fetus should be presumed viable if a heartbeat is audible using

a stethoscope. The fetus which is to be aborted before the heartbeat is audible

should be regarded as potentially viable until the abortion procedure is actually

in progress, after which it may be considered nonviable.

59

VIII.

DELIBERATIONS AND CONCLUSIONS

The charge to the Commission is to investigate and study research involving

the living fetus and to make recommendations to the Secretary, DHEW, on "policies

defining the circumstances (if any) under which such research may be conducted or

supported." The Commission has attempted to fulfill that duty by conducting

investigations into research on the fetus and by providing a public forum for the

presentation and analysis of views on this subject. It must be recognized that

the Commission was placed under severe limitations of time by its Congressional

mandate. As a result, these considerations on research involving fetuses have

necessarily been developed prior to the Commission's larger task of studying the

nature of research, the basic ethical principles which should guide it, the prob-

lem of informed consent and the review process.

After the Commission identified the information that was required for ade-

quate consideration of the charge, a compendium of pertinent scientific literature

and medical experience was prepared by consultants and contractors. In addition,

a broad range of views was presented in letters, reports and testimony by theo-

logians, philosophers, physicians, scientists, lawyers, public officials and

private citizens. The Commission then undertook critical analysis of the studies

and presentations, and conducted public deliberations on the issues involved.

Finally, the Commission formulated its Recommendations.

This section of the Commission's report summarizes the reasoning and con-

clusions that emerged during the deliberations. Section IX of the report sets

forth the Commission's Recommendations to the Secretary, DHEW. These Recommenda-

tions arise from and are consistent with the Deliberations and Conclusions of the

Commission. The Recommendations should be considered only within the context of

the Deliberations that precede them.

A. Preface to Deliberations and Conclusions. Throughout the deliberations

of the Commission, the belief has been affirmed that the fetus as a human subject

61

is deserving of care and respect. Although the Commission has not addressed

directly the issues of the personhood and the civil status of the fetus, the

members of the Commission are convinced that moral concern should extend to all

who share human genetic heritage, and that the fetus, regardless of life pros-

pects, should be treated respectfully and with dignity.

The members of the Commission are also convinced that medical research has

resulted in significant improvements in the care of the unborn threatened by

death or disease, and they recognize that further progress is anticipated. Within

the broad category of medical research, however, public concern has been expressed

with regard to the nature and necessity of research on the human fetus. The evi-

dence presented to the Commission was based upon a comprehensive search of the

world's literature and a review of more than 3000 communications in scientific

periodicals. The preponderance of all research involved experimental procedures

designed to benefit directly a fetus threatened by premature delivery, disease or

death, or to elucidate normal processes or development. Some research constituted

an element in the health care of pregnant women. Other research involved only

observation or the use of noninvasive procedures bearing little or no risk. A

final class of investigation (falling outside the present mandate of the Commission)

has made use of tissues of the dead fetus, in accordance with accepted standards

for treatment of the human cadaver. The Commission finds that, to the best of

its knowledge, these types of research have not contravened accepted ethical

standards.

Nonetheless, the Commission notes that there have been instances of abuse

in the area of fetal research. Moreover, differences of opinion exist as to

whether desired results could have been attained without the use of the human

fetus in nontherapeutic research.

Concern has also been expressed that the poor and minority groups may bear

an inequitable burden as research subjects. The Commission believes that those

groups which are most vulnerable to inequitable treatment should receive special

protection.

The Commission concludes that some information which is in the public

interest and which provides significant advances in health care can be attained

only through the use of the human fetus as a research subject. The Recommendations

62

which follow express the Commission's belief that, while the exigencies of

research and the moral imperatives of fair and respectful treatment may appear

to be mutually limiting, they are not incompatible.

B. Ethical Principles and Requirements Governing Research on Human Subjects

with Special Reference to the Fetus and the Pregnant Woman. The Commission has

a mandate to develop the ethical principles underlying the conduct of all research

involving human subjects. Until it can adequately fulfill this charge, its state-

ment of principles is necessarily limited. In the interim, it proposes the fol-

lowing as basic ethical principles for use of human subjects in general, and

research involving the fetus and the pregnant woman in particular.

Scientific inquiry is a distinctly human endeavor. So, too, is the pro-

tection of individual integrity. Freedom of inquiry and the social benefits

derived therefrom, as well as protection of the individual are valued highly and

are to be encouraged. For the most part, they are compatible pursuits. When

occasionally they appear to be in conflict, efforts must be made through public

deliberation to effect a resolution.

In effecting this resolution, the integrity of the individual is preeminent.

It is therefore the duty of the Commission to specify the boundaries that respect

for the fetus must impose upon freedom of scientific inquiry. The Commission has

considered the principles proposed by ethicists in relation to the exigencies of

scientific inquiry, the requirements and present limitations of medical practice,

and legal commentary. Among the general principles for research on human subjects

judged to be valid and binding are: (1) to avoid harm whenever possible, or at

least to minimize harm; (2) to provide for fair treatment by avoiding discrim-

ination between classes or among members of the same class; and (3) to respect the

integrity of human subjects by requiring informed consent. An additional principle

pertinent to the issue at hand is to respect the human character of the fetus.

To this end, the Commission concludes that in order to be considered ethi-

cally acceptable, research involving the fetus should be determined by adequate

review to meet certain general requirements:

(1) Appropriate prior investigations using animal models and non-

pregnant humans must have been completed.

63

(2) The knowledge to be gained must be important and obtainable by

no reasonable alternative means.

(3) Risks and benefits to both the mother and the fetus must have

been fully evaluated and described.

(4) Informed consent must be sought and granted under proper conditions.

(5) Subjects must be selected so that risks and benefits will not fall

inequitably among economic, racial, ethnic and social classes.

These requirements apply to all research on the human fetus. In the

application of these principles, however, the Commission found it helpful to con-

sider the following distinctions: (1) therapeutic and nontherapeutic research;

(2) research directed toward the pregnant woman and that directed toward the

fetus; (3) research involving the fetus-going-to-term and the fetus-to-be-aborted;

(4) research occurring before, during or after an abortion procedure; and

(5) research which involves the nonviable fetus ex utero and that which involves

the possibly viable infant. The first two distinctions encompass the entire period

of the pregnancy through delivery; the latter three refer to different portions

of the developmental continuum.

The Commission observes that the fetus is sometimes an unintended subject

of research when a woman participating in an investigation is incorrectly pre-

sumed not to be pregnant. Care should be taken to minimize this possibility.

C. Application to Research Involving the Fetus. The application of the

general principles enumerated above to the use of the human fetus as a research

subject presents problems because the fetus cannot be a willing participant in

experimentation. As with children, the comatose and other subjects unable to

consent, difficult questions arise regarding the balance of risk and benefit and

the validity of proxy consent.

In particular, some would question whether subjects unable to consent

should ever be subjected to risk in scientific research. However, there is

general agreement that where the benefits as well as the risks of research accrue

to the subject, proxy consent may be presumed adequate to protect the subject's

interests. The more difficult case is that where the subject must bear risks

without direct benefit.

64

The Commission has not yet studied the issues surrounding informed consent

and the validity of proxy consent for nontherapeutic research (including the

difficult issue of consent by a pregnant minor). These problems will be explored

under the broader mandate of the Commission. In the interim, the Commission has

taken various perspectives into consideration in its deliberations about the use

of the fetus as a subject in different research settings. The Deliberations and

Conclusions of the Commission regarding the application of general principles to

the use of the fetus as a human subject in scientific research are as follows:

1. In therapeutic research directed toward the fetus, the fetal sub-

ject is selected on the basis of its health condition, benefits and risks accrue

to that fetus, and proxy consent is directed toward that subject's own welfare.

Hence, with adequate review to assess scientific merit, prior research, the

balance of risks and benefits, and the sufficiency of the consent process, such

research conforms with all relevant principles and is both ethically acceptable

and laudable. In view of the necessary involvement of the woman in such research,

her consent is considered mandatory; in view of the father's possible ongoing

responsibility, his objection is considered sufficient to veto.

2. Therapeutic research directed toward the pregnant woman may expose

the fetus to risk for the benefit of another subject and thus is at first glance

more problematic. Recognizing the woman's priority regarding her own health care,

however, the Commission concludes that such research is ethically acceptable pro-

vided that the woman has been fully informed of the possible impact on the fetus

and that other general requirements have been met. Protection for the fetus is

further provided by requiring that research put the fetus at minimum risk con-

sistent with the provision of health care for the woman. Moreover, therapeutic

research directed toward the pregnant woman frequently benefits the fetus, though

it need not necessarily do so. In view of the woman's right to privacy regarding

her own health care, the Commission concludes that the informed consent of the

woman is both necessary and sufficient.

In general, the Commission concludes that therapeutic research directed

toward the health condition of either the fetus or the pregnant woman is, in

principle, ethical. Such research benefits not only the individual woman or

65

fetus but also women and fetuses as a class, and should therefore be encouraged

actively.

The Commission, in making recommendations on therapeutic and nontherapeutic

research directed toward the pregnant woman, (Recommendations (2) and (3)), in

no way intends to preclude research on improving abortion techniques otherwise

permitted by law and government regulation.

3. Nontherapeutic research directed toward the fetus in utero or

toward the pregnant woman poses difficult problems because the fetus may be

exposed to risk for the benefit of others.

Here, the Commission concludes that where no additional risks are imposed

on the fetus (e.g., where fluid withdrawn during the course of treatment is used

additionally for nontherapeutic research), or where risks are so minimal as to

be negligible, proxy consent by the parent(s) is sufficient to provide protection.

(Hence, the consent of the woman is sufficient provided the father does not

object.) The Commission recognizes that the term "minimal" involves a value

judgment and acknowledges that medical opinion will differ regarding what con-

stitutes "minimal risk." Determination of acceptable minimal risk is a function

of the review process.

When the risks cannot be fully assessed, or are more than minimal, the

situation is more problematic. The Commission affirms as a general principle

that manifest risks imposed upon nonconsenting subjects cannot be tolerated.

Therefore, the Commission concludes that only minimal risk can be accepted as

permissible for nonconsenting subjects in nontherapeutic research.

The Commission affirms that the woman's decision for abortion does not,

in itself, change the status of the fetus for purposes of protection. Thus, the

same principles apply whether or not abortion is contemplated; in both cases,

only minimal risk is acceptable.

Differences of opinion have arisen in the Commission, however, regarding

the interpretation of risk to the fetus-to-be-aborted and thus whether some

experiments that would not be permissible on a fetus-going-to-term might be

permissible on a fetus-to-be-aborted. Some members hold that no procedures

should be applied to a fetus-to-be-aborted that would not be applied to a

66

fetus-going-to-term. Indeed, it was also suggested that any research involving

fetuses-to-be-aborted must also involve fetuses-going-to-term. Others argue

that, while a woman's decision for abortion does not change the status of the

fetus per se, it does make a significant difference in one respect--namely, in

the risk of harm to the fetus. For example, the injection of a drug which

crosses the placenta may not injure the fetus which is aborted within two weeks

of injection, where it might injure the fetus two months after injection. There

is always, of course, the possibility that a woman might change her mind about

the abortion. Even taking this into account, however, some members argue that

risks to the fetus-to-be-aborted may be considered "minimal" in research which

would entail more than minimal risk for a fetus-going-to-term.

There is basic agreement among Commission members as to the validity of

the equality principle. There is disagreement as to its application to indivi-

dual fetuses and classes of fetuses. Anticipating that differences of inter-

pretation will arise over the application of the basic principles of equality

and the determination of "minimal risk," the Commission recommends review at

the national level. The Commission believes that such review would provide the

appropriate forum for determination of the scientific and public merit of such

research. In addition, such review would facilitate public discussion of the

sensitive issues surrounding the use of vulnerable nonconsenting subjects in

research.

The question of consent is a complicated one in this area of research.

The Commission holds that procedures that are part of the research design should

be fully disclosed and clearly distinguished from those which are dictated by

the health care needs of the pregnant woman or her fetus. Questions have been

raised regarding the validity of parental proxy consent where the parent(s)

have made a decision for abortion. The Commission recognizes that unresolved

problems both of law and of fact surround this question. It is the considered

opinion, however, that women who have decided to abort should not be presumed

to abandon thereby all interest in and concern for the fetus. In view of the

close relationship between the woman and the fetus, therefore, and the necessary

involvement of the woman in the research process, the woman's consent is con-

sidered necessary. The Commission is divided on the question of whether her

consent alone is sufficient. Assignment of an advocate for the fetus was proposed

67

as an additional safeguard; this issue will be thoroughly explored in connection

with the Commission's review of the consent process. Most of the Commissioners

agree that in view of the father's possible responsibility for the child, should

it be brought to term, the objection of the father should be sufficient to veto.

Several Commissioners, however, hold that for nontherapeutic research directed

toward the pregnant woman, the woman's consent alone should be sufficient and

the father should have no veto.

4. Research on the fetus during the abortion procedure or on the

nonviable fetus ex utero raises sensitive problems because such a fetus must be

considered a dying subject. By definition, therefore, the research is nonthera-

peutic in that the benefits will not accrue to the subject. Moreover, the

question of consent is complicated because of the special vulnerability of the

dying subject.

The Commission considers that the status of the fetus as dying alters the

situation in two ways. First, the question of risk becomes less relevant, since

the dying fetus cannot be "harmed" in the sense of "injured for life." Once the

abortion procedure has begun, or after it is completed, there is no chance of a

change of mind on the woman's part which will result in a living, injured subject.

Second, however, while questions of risk become less relevant, considerations of

respect for the dignity of the fetus continue to be of paramount importance, and

require that the fetus be treated with the respect due to dying subjects. While

dying subjects may not be "harmed" in the sense of "injured for life," issues

of violation of integrity are nonetheless central. The Commission concludes,

therefore, that out of respect for the dying subjects, no nontherapeutic inter-

ventions are permissible which would alter the duration of life of the nonviable

fetus ex utero.

Additional protection is provided by requiring that no significant changes

are made in the abortion procedure strictly for purposes of research. The Com-

mission was divided on the question of whether a woman has a right to accept

modifications in the timing or method of the abortion procedure in the interest

of research, and whether the investigator could ethically request her to do so.

Some Commission members desired that neither the research nor the investigator

in any way influence the abortion procedure; others felt that modifications in

68

timing or method of abortion were acceptable provided no new elements of risk

were introduced. Still others held that even if modifications increased the

risk, they would be acceptable provided the woman had been fully informed of

all risks, and provided such modifications did not postpone the abortion beyond

the twentieth week of gestational age (five lunar months, four and one-half

calendar months). Despite this division of opinion, the Recommendation of the

Commission on this matter is that the design and conduct of a nontherapeutic

research protocol should not determine the recommendations by a physician

regarding the advisability, timing or method of abortion. No members of the

Commission desired less stringent measures.

Furthermore, it is possible that, due to mistaken estimation of gesta-

tional age, an abortion may issue in a possibly viable infant. If there is any

danger that this might happen, research which would entail more than minimal

risk would be absolutely prohibited. In order to avoid that possibility the

Commission recommends that, should research during abortion be approved by

national review, it be always on condition that estimated gestational age be

below 20 weeks. There is, of course, a moral and legal obligation to attempt

to save the life of a possibly viable infant.

Finally, the Commission has been made aware that certain research, par-

ticularly that involving the living nonviable fetus, has disturbed the moral

sensitivity of many persons. While it believes that its Recommendations would

preclude objectionable research by adherence to strict review processes, prob-

lems of interpretation or application of the Commission's Recommendations may

still arise. In that event, the Commission proposes ethical review at a

national level in which informed public disclosure and assessment of the prob-

lems, the type of proposed research and the scientific and public importance

of the expected results can take place.

D. Review Procedures. The Commission will conduct comprehensive studies

of existing review mechanisms in connection with its broad mandate to develop

guidelines and make recommendations concerning ethical issues involved in

research on human subjects. Until the Commission has completed these studies,

it can offer only tentative conclusions and recommendations regarding review

mechanisms.

69

In the interim, the Commission finds that existing review procedures

required by statute (P.L. 93-348) and DHEW regulations (45 CFR 46) suffice for

all therapeutic research involving the pregnant woman and the fetus, and for

all nontherapeutic research which imposes minimal or no risk and which would

be acceptable for conduct on a fetus in utero to be carried to term or on

an infant. Guidelines to be employed under the existing review procedures

include: (1) importance of the knowledge to be gained; (2) completion of appro-

priate studies on animal models and nonpregnant humans and existence of no rea-

sonable alternative; (3) full evaluation and disclosure of the risks and bene-

fits that are involved; and (4) supervision of the conditions under which consent

is sought and granted, and of the information that is disclosed during that

process.

The case is different, however, for nontherapeutic research directed

toward a pregnant woman or a fetus if it involves more than minimal risk or

would not be acceptable for application to an infant. Questions may arise

concerning the definition of risk or the assessment of scientific and public

importance of the research. In such cases, the Commission considers current

review procedures insufficient. It recommends these categories be reviewed

by a national review body to determine whether the proposed research could be

conducted within the spirit of the Commission's recommendations. It would

interpret these recommendations and apply them to the proposed research, and

in addition, assess the scientific and public value of the anticipated results

of the investigation.

The national review panel should be composed of individuals having

diverse backgrounds, experience and interests, and be so constituted as to be

able to deal with the legal, ethical, and medical issues involved in research

on the human fetus. In addition to the professions of law, medicine, and the

research sciences, there should be adequate representation of women, members

of minority groups, and individuals conversant with the various ethical per-

suasions of the general community.

Inasmuch as even such a panel cannot always judge public attitudes, panel

meetings should be open to the public, and, in addition, public participation

through written and oral submissions should be sought.

70

E. Compensation. The Commission expressed a strong conviction that

considerable attention be given to the issue of provision of compensation to

those who may be injured as a consequence of their participation as research

subjects.

Concerns regarding the use of inducements for participation in research

are only partially met by the Commission's Recommendation (14) on the prohibi-

tion of the procurement of an abortion for research purposes. Compensation

not only for injury from research but for participation in research as a normal

volunteer or in a therapeutic situation will be part of later Commission delib-

erations.

F. Research Conducted Outside the United States. The Commission has

considered the advisability of modifying its standards for research which is

supported by the Secretary, DHEW, and is conducted outside the United States.

It has concluded that its recommendations should apply as a single minimal

standard, but that research should also comply with any more stringent limita-

tions imposed by statutes or standards of the country in which the research will

be conducted.

G. The Moratorium on Fetal Research. The Commission notes that the

restrictions on fetal research (imposed by Section 213 of P.L. 93-348) have been

construed broadly throughout the research community, with the result that ethi-

cally acceptable research, which might yield important biomedical information,

has been halted. For this reason, it is considered in the public interest that

the moratorium be lifted immediately, that the Secretary take special care

thereafter that the Commission's concerns for the protection of the fetus as a

research subject are met, and appropriate regulations based upon the Commission's

recommendations be implemented within a year from the date of submission of this

report to the Secretary, DHEW. Until final regulations are published, the

existing review panels at the agency and institutional levels should utilize

the Deliberations and Recommendations of the Commission in evaluating the accept-

ability of all grant and contract proposals submitted for funding.

71

H. Synthesis. The Commission concludes that certain prior conditions

apply broadly to all research involving the fetus, if ethical considerations are

to be met. These requirements include evidence of pertinent investigations in

animal models and nonpregnant humans, lack of alternative means to obtain the

information, careful assessment of the risks and benefits of the research, and

procedures to ensure that informed consent has been sought and granted under

proper conditions. Determinations as to whether these essential requirements

have been met may be made under existing review procedures, pending study by

the Comission of the entire review process.

In the judgment of the Commission, therapeutic research directed toward

the health care of the pregnant woman or the fetus raises little concern, pro-

vided it meets the essential requirements for research involving the fetus, and

is conducted under appropriate medical and legal safeguards.

For the most part, nontherapeutic research involving the fetus to be

carried to term or the fetus before, during or after abortion is acceptable so

long as it imposes minimal or no risk to the fetus and, when abortion is involved,

imposes no change in the timing or procedure for terminating pregnancy which

would add any significant risk. When a research protocol or procedure presents

special problems of interpretation or application of these guidelines, it should

be subject to national ethical review; and it should be approved only if the

knowledge to be gained is of medical importance, can be obtained in no other

way, and the research proposal does not offend community sensibilities.

IX.

RECOMMENDATIONS

1. Therapeutic research directed toward the fetus may be conducted or

supported, and should be encouraged, by the Secretary, DHEW, provided such

research (a) conforms to appropriate medical standards, (b) has received the

informed consent of the mother, the father not dissenting, and (c) has been

approved by existing review procedures with adequate provision for the monitoring

of the consent process. (Adopted unanimously.)

2. Therapeutic research directed toward the pregnant woman may be con-

ducted or supported, and should be encouraged, by the Secretary, DHEW, provided

such research (a) has been evaluated for possible impact on the fetus, (b) will

place the fetus at risk to the minimum extent consistent with meeting the health

needs of the pregnant woman, (c) has been approved by existing review procedures

with adequate provision for the monitoring of the consent process, and (d) the

pregnant woman has given her informed consent. (Adopted unanimously.)

3. Nontherapeutic research directed toward the pregnant woman may be

conducted or supported by the Secretary, DHEW, provided such research (a) has

been evaluated for possible impact on the fetus, (b) will impose minimal or no

risk to the well-being of the fetus, (c) has been approved by existing review

procedures with adequate provision for the monitoring of the consent process,

(d) special care has been taken to assure that the woman has been fully informed

regarding possible impact on the fetus, and (e) the woman has given informed

consent. (Adopted unanimously.)

It is further provided that nontherapeutic research directed at the preg-

nant woman may be conducted or supported (f) only if the father has not objected,

both where abortion is not at issue (adopted by a vote of 8 to 1) and where an

abortion is anticipated (adopted by a vote of 5 to 4).

73

4. Nontherapeutic research directed toward the fetus in utero (other

than research in anticipation of, or during, abortion) may be conducted or sup-

ported by the Secretary, DHEW, provided (a) the purpose of such research is the

development of important biomedical knowledge that cannot be obtained by alter-

native means, (b) investigation on pertinent animal models and nonpregnant humans

has preceded such research, (c) minimal or no risk to the well-being of the fetus

will be imposed by the research, (d) the research has been approved by existing

review procedures with adequate provision for the monitoring of the consent pro-

cess, (e) the informed consent of the mother has been obtained, and (f) the

father has not objected to the research. (Adopted unanimously.)

5. Nontherapeutic research directed toward the fetus in anticipation of

abortion may be conducted or supported by the Secretary, DHEW, provided such

research is carried out within the guidelines for all other nontherapeutic

research directed toward the fetus in utero. Such research presenting special

problems related to the interpretation or application of these guidelines may

be conducted or supported by the Secretary, DHEW, provided such research has

been approved by a national ethical review body. (Adopted by a vote of 8 to 1.)

6. Nontherapeutic research directed toward the fetus during the abortion

procedure and nontherapeutic research directed toward the nonviable fetus

ex utero may be conducted or supported by the Secretary, DHEW, provided (a) the

purpose of such research is the development of important biomedical knowledge

that cannot be obtained by alternative means, (b) investigation on pertinent ani-

mal models and nonpregnant humans (when appropriate) has preceded such research,

(c) the research has been approved by existing review procedures with adequate

provision for the monitoring of the consent process, (d) the informed consent of

the mother has been obtained, and (e) the father has not objected to the research;

and provided further that (f) the fetus is less than 20 weeks gestational age,

(g) no significant procedural changes are introduced into the abortion procedure

in the interest of research alone, and (h) no intrusion into the fetus is made

which alters the duration of life. Such research presenting special problems

related to the interpretation or application of these guidelines may be conducted

or supported by the Secretary, DHEW, provided such research has been approved by

a national ethical review body. (Adopted by a vote of 8 to 1.)

74

7. Nontherapeutic research directed toward the possibly viable infant

may be conducted or supported by the Secretary, DHEW, provided (a) the purpose

of such research is the development of important biomedical knowledge that cannot

be obtained by alternative means, (b) investigation on pertinent animal models

and nonpregnant humans (when appropriate) has preceded such research, (c) no

additional risk to the well-being of the infant will be imposed by the research,

(d) the research has been approved by existing review procedures with adequate

provision for the monitoring of the consent process, and (e) informed consent

of either parent has been given and neither parent has objected. (Adopted

unanimously.)

8. Review Procedures. Until the Commission makes its recommendations

regarding review and consent procedures, the review procedures mentioned above

are to be those presently required by the Department of Health, Education, and

Welfare. In addition, provision for monitoring the consent process shall be

required in order to ensure adequacy of the consent process and to prevent unfair

discrimination in the selection of research subjects, for all categories of

research mentioned above. A national ethical review, as required in Recommenda-

tions (5) and (6), shall be carried out by an appropriate body designated by the

Secretary, DHEW, until the establishment of the National Advisory Council for

the Protection of Subjects of Biomedical and Behavioral Research. In order to

facilitate public understanding and the presentation of public attitudes toward

special problems reviewed by the national review body, appropriate provision

should be made for public attendance and public participation in the national

review process. (Adopted unanimously, one abstention.)

9. Research on the Dead Fetus and Fetal Tissue. The Commission recommends

that use of the dead fetus, fetal tissue and fetal material for research purposes

be permitted, consistent with local law, the Uniform Anatomical Gift Act and com-

monly held convictions about respect for the dead. (Adopted unanimously, one

abstention.)

10. The design and conduct of a nontherapeutic research protocol should

not determine recommendations by a physician regarding the advisability, timing

or method of abortion. (Adopted by a vote of 6 to 2.)

75

11. Decisions made by a personal physician concerning the health care

of a pregnant woman or fetus should not be compromised for research purposes,

and when a physician of record is involved in a prospective research protocol,

independent medical judgment on these issues is required. In such cases, review

panels should assure that procedures for such independent medical judgment are

adequate, and all conflict of interest or appearance thereof between appropriate

health care and research objectives should be avoided. (Adopted unanimously.)

12. The Commission recommends that research on abortion techniques con-

tinue as permitted by law and government regulation. (Adopted by a vote of

6 to 2.)

13. The Commission recommends that attention be drawn to Section 214(d)

of the National Research Act (P.L. 93-348) which provides that:

"No individual shall be required to perform or assist in the performance of any part of a health service program or research activity funded in whole or in part by the Secre- tary of Health, Education, and Welfare if his performance or assistance in the performance of such part of such pro- gram or activity would be contrary to his religious beliefs or moral convictions."

(Adopted unanimously.)

14. No inducements, monetary or otherwise, should be offered to procure

an abortion for research purposes. (Adopted unanimously.)

15. Research which is supported by the Secretary, DHEW, to be conducted

outside the United States should at the minimum comply in full with the standards

and procedures recommended herein. (Adopted unanimously.)

16. The moratorium which is currently in effect should be lifted immedi-

ately, allowing research to proceed under current regulations but with the

application of the Commission's Recommendations to the review process. All the

foregoing Recommendations of the Commission should be implemented as soon as the

Secretary, DHEW, is able to promulgate regulations based upon these Recommenda-

tions and the public response to them. (Adopted by a vote of 9 to 1.)

76

DISSENTING STATEMENT OF COMMISSIONER DAVID W. LOUISELL

I am compelled to disagree with the Commission's Recommendations (and

the reasoning and definitions on which they are based) insofar as they succumb

to the error of sacrificing the interests of innocent human life to a postulated

social need. I fear this is the inevitable result of Recommendations (5) and

(6). These would permit nontherapeutic research on the fetus in anticipation of

abortion and during the abortion procedure, and on a living infant after abortion

when the infant is considered nonviable, even though such research is precluded

by recognized norms governing human research in general. Although the Commission

uses adroit language to minimize the appearance of violating standard norms, no

facile verbal formula can avoid the reality that under these Recommendations the

fetus and nonviable infant will be subjected to nontherapeutic research from

which other humans are protected.

I disagree with regret, not only because of the Commission's zealous

efforts but also because there is significant good in its Report especially its

showing that much of the research in this area is therapeutic for the individuals

involved, both born and unborn, and hence of unquestioned morality when based on

prudent medical judgment. The Report also makes clear that some research, even

though nontherapeutic, is merely observational or otherwise without significant

risk to the subject, and therefore is within standard human research norms and

as unexceptional morally as it is useful scientifically.

But the good in much of the Report cannot blind me to its departure from

our society's most basic moral commitment: the essential equality of all human

beings. For me the lessons of history are too poignant, and those of this cen-

tury too fresh, to ignore another violation of human integrity and autonomy by

subjecting unconsenting human beings, whether or not viable, to harmful research

even for laudable scientic purposes.

Admittedly, the Supreme Court's rationale in its abortion decisions of

1973-- Roe v . Wade and Doe v . Bolton , 310 U.S. 113, 179--has given this Commis-

sion an all but impossible task. For many see in that rationale a total negation

of fetal rights, absolutely so for the first two trimesters and substantially

77

so for the third. The confusion is understandable, rooted as it is in the

Court's invocation of the specially constructed legal fiction of "potential"

human life, its acceptance of the notion that human life must be "meaningful" in

order to be deserving of legal protection, and its resuscitation of the concept

of partial human personhood, which had been thought dead in American society

since the demise of the Dredd Scott decision. Little wonder that intelligent

people are asking: how can one who has no right to life itself have the lesser

right of precluding experimentation on his or her person?

It seems to me that there are at least two compelling answers to the

notion that Roe and Doe have placed fetal experimentation, and experimentation

on nonviable infants, altogether outside the established protections for human

experimentation. First, while we must abide the Court's mandate in a particular

case on the issues actually decided even though the decision is wrong and in fact

only an exercise of "raw judicial power" (White, J., dissenting in Roe and Doe ),

this does not mean we should extend an erroneous rationale to other situations.

To the contrary, while seeking to have the wrong corrected by the Court itself,

or by the public, the citizen should resist its extension to other contexts.

As Abraham Lincoln, discussing the Dredd Scott decision, put it:

"(T)he candid citizen must confess that if the policy of the government upon vital questions affecting the whole people, is to be irrevocably fixed by decisions of the Supreme Court, the instant that they are made, in ordinary litigation between parties in personal actions, the people will have ceased to be their own rulers, having, to that extent, practically resigned their government, into the hands of that eminent tribunal." (4 Basler, The Collected Works of Abraham Lincoln 262, 268 (1963).)

Thus even if the Court had intended by its Roe and Doe rationale to exclude the

unborn, and newly born nonviable infants, from all legal protection including

that against harmful experimentation, I can see no legal principle which would

justify, let alone require, passive submission to such a breach of our moral

tradition and commitment.

Secondly, the Court in Roe and Doe did not have before it, and presum-

ably did not intend to pass upon and did not in fact pass upon, the question of

experimentation on the fetus or born infant. Certainly that question was not

78

directly involved in those cases. Granting the fullest intendment to those

decisions possibly arguable, it seems to me that the woman's new-found constitu-

tional right of privacy is fulfilled upon having the fetus aborted. If an infant

survives the abortion, there is hardly an additional right of privacy to then

have him or her killed or harmed in any way, including harm by experimentation

impermissible under standard norms. At least Roe and Doe should not be assumed

to recognize such a right. And while the Court's unfortunate language respecting

"potential" and "meaningful" life is thought by some to imply a total abandonment

of in utero life for all legal purposes, at least for the first two trimesters,

such a conclusion would so starkly confront our social, legal, and moral tradi-

tions that I think we should not assume it. To the contrary we should assume

that the language was limited by the abortion context in which used and was not

intended to effect a departure from the limits on human experimentation univer-

sally recognized at least in principle.

A shorthand way, developed during the Commission's deliberations, of

stating the principle that would adhere to recognized human experimentation norms

and that should be recommended in place of Recommendation (5) is: No research

should be permitted on a fetus-to-be-aborted that would not be permitted on one

to go to term. This principle is essential if all of the unborn are to have the

protection of recognized limits on human experimentation. Any lesser protection

violates the autonomy and integrity of the fetus, and even a decision to have an

abortion cannot justify ignoring this fact. There is not only the practical

problem of a possible change of mind by the pregnant woman. For me, the chief

vice of Recommendation (5) is that it permits an escape hatch from human experi-

mentation principles merely by decision of a national ethical review body. No

principled basis for an exception has been, nor in my judgment can be, formulated.

The argument that the fetus-to-be-aborted "will die anyway" proves too much. All

of us "will die anyway." A woman's decision to have an abortion, however pro-

tected by Roe and Doe in the interests of her privacy or freedom of her own body,

does not change the nature or quality of fetal life.

Recommendation (6) concerns what is now called the "nonviable fetus

ex utero " but which up to now has been known by the law, and I think by society

generally, as an infant, however premature. This Recommendation is unacceptable

to me because, on approval of a national review body, it makes certain infants

79

up to five months gestational age potential research material, provided the

mother who has of course consented to the abortion, also consents to the experi-

mentation and the father has not objected. In my judgment all infants, however

premature or inevitable their death, are within the norms governing human experi-

mentation generally. We do not subject the aged dying to unconsented experi-

mentation, nor should we the youthful dying.

Both Recommendations (5) and (6) have the additional vice of giving

the researcher a vested interest in the actual effectuation of a particular

abortion, and society a vested interest in permissive abortion in general.

I would, therefore, turn aside any approval, even in science's name,

that would by euphemism or other verbal device, subject any unconsenting human

being, born or unborn, to harmful research, even that intended to be good for

society. Scientific purposes might be served by nontherapeutic research on

retarded children, or brain dissection of the old who have ceased to lead "mean-

ingful" lives, but such research is not proposed--at least not yet. As George

Bernard Shaw put it in The Doctor's Dilemma: "NO man is allowed to put his

mother in the stove because he desires to know how long an adult woman will sur-

vive the temperature of 500 degrees Fahrenheit, no matter how important or inter-

esting that particular addition to the store of human knowledge may be." Is it

the mere youth of the fetus that is thought to foreclose the full protection of

established human experimentation norms? Such reasoning would imply that a child

is less deserving of protection than an adult. But reason, our tradition, and

the U.N. Declaration of Human Rights all speak to the contrary, emphasizing the

need of special protection for the young.

Even if I were to approach my task as a Commissioner from a utilitarian

viewpoint only, I would have to say that on the record here I am not convinced

that an adequate showing has been made of the necessity for nontherapeutic fetal

experimentation in the Scientific or social interest. The Commission's reliance

is on the Battelle Report and its reliance is misplaced. The relevant Congres-

sional mandate was to conduct an investigation and study of the alternative means

for achieving the purposes of fetal research (P.L. 93-348, July 12, 1974,

Sec. 202(b): National Research Act).

80

As Commissioner Robert E. Cooke, M.D., who is sophisticated in research

procedures, pointed out in his Critique of the Battelle Report: "The only true

objective approach beyond question, since scientists make [the analysis of the

necessity for nontherapeutic fetal research], is to collect information and ana-

lyze past research accomplishments with the intention of disproving, not proving

the hypothesis that research utilizing the living human fetus nonbeneficially is

necessary." The Battelle Report seems to me not in accord with the Congressional

intention in that it proceeds from a viewpoint opposite to that quoted, and is

really an effort to prove the indispensability of nontherapeutic research. In

any event, if that is its purpose, it fails to achieve it, for most of what it

claims to have been necessary could be justified as therapeutic research or at

least as noninvasive of the fetus (e.g., probably amniocentesis). In view of

haste with which this statement must be prepared if it is to accompany the Com-

mission's report, rather than enlarge upon these views now I refer both to the

Cooke Critique and the Battelle Report itself both-of which I am informed will

be a part of or appended to the Commission's Report.

An emotional plea was made at the Commission's hearings not to acknowledge

limitations on experimentation that would inhibit the court-granted permissive

abortion. However, until its last meeting, I think the Commission for the most

part admirably resisted the temptation to distort its purpose by pro-abortion

advocacy. But at the last meeting, without prior preparation or discussion, it

adopted Recommendation (12) promotive of research on abortion techniques. This

I feel is not germane to our task, is imprudent and certainly was not adequately

considered.

Finally, I do not think that the Commission should urge lifting the mora-

torium on fetal research as stated in Recommendation (16). To the extent that

duration of the moratorium is controlled by Section 213 of the National Research

Act, the subject is beyond our control and we ought not assume authority that is

not ours. This is matter not for us and not, ultimately, for any administrative

official, but for Congress. If the American people as a democratic society

really intend to withdraw from the fetus and nonviable infant the protection of

the established principles governing human experimentation, that action I feel

should come from the Congress of the United States, in the absence of a practical

way to have a national vote. Assuming that any representative voice is adequate

81

to bespeak so basic and drastic a change in the public philosophy of the United

States, it could only be the voice of Congress. Of course there is no reason

why the Secretary of DHEW cannot immediately make clear that no researcher need

stand in fear of therapeutic research.

As noted at the outset, the Commission's work has achieved some good

results in reducing the possibilities of manifest abuses and thereby according

a measure of protection to humans at risk by reason of research. That it has

not been more successful is in my judgment not due so much to the Commission's

failings as to the harsh and pervasive reality that American society is itself

at risk--the risk of losing its dedication "to the proposition that all men are

created equal." We may have to learn once again that when the bell tolls for

the lost rights of any human being, even the politically weakest, it tolls for

all.

David W. Louisell Elizabeth Josselyn Boalt Professor of Law University of California, Berkeley

82

STATEMENT OF COMMISSIONER KAREN LEBACQZ, WITH THE CONCURRENCE OF COMMISSIONER ALBERT R. JONSEN

ON THE FIRST ITEM

The following comments include some points of dissent from the Recommen-

dations of the Commission. For the most part, however, these comments are

intended as elaborations on the Report rather than dissent from it.

1. At several points, the Commission established as a criterion for

permissible research an acceptable level of risk--e.g., "no risk" or "minimal

risk." I support the Commission's Recommendations regarding such criteria, but

I wish to make several interpretative comments.

First, I think it should be stressed that in the first trials on human

subjects or on a new class of human subjects, the risks are almost always

unknown. The Commission heard compelling evidence that differences in physiology

and pharmacology between human and other mammalian fetuses are such that even

with substantial trials in animal models it is often not possible to assess the

risks for the first trials with human fetuses. For example, evidence from ani-

mal trials in the testing of thalidomide provided grounds for an estimation of

low risk to human subjects; the initial trials in the human fetus resulted in

massive teratogenic effects.

I would therefore urge review boards to exercise caution in the interpre-

tation of "risk" and to avoid the temptation to consider the risks "minimal"

when in fact they cannot be fully assessed.

Second, I think it important to emphasize the evaluative nature of judg-

ments of risk. The term "risk" means chance of harm. Interpretation of risk

involves both an assessment of statistical chance of injury and an assessment

of the nature of the injury. Value judgments about what constitutes a "harm"

and what percentage chance of harm is acceptable are both involved in the deter-

mination of acceptable risk. A small chance of great harm may be considered

unacceptable where a greater chance of a smaller harm would be acceptable. For

example, it is commonly accepted that a 1-2 percent chance of having a child with

Down's syndrome is a "high" risk, where the same chance of minor infection from

83

amniocentesis would be considered a "low" risk. Opinions will differ both

about what constitutes "harm" or injury and also about what chance of a partic-

ular harm is acceptable.

For all these reasons, the interpretation of risk and the designation

of acceptable "minimal risk" merit considerable attention by the scientific

community and the lay public. The provision of national review in problematic

instances should engender serious deliberation on these critical issues.

Third, the establishment of criteria for "no risk" or "minimal risk" is

obviously related to the interpretation of "harm." In general, the Commission has discussed "harm" in terms of two indices: (1) injury or diminished faculty,

and (2) pain. A third commonly accepted definition of "harm" is "offense against

right or morality"; this meaning of harm has been subsumed under the rubric of

violation of dignity or integrity of the fetus, and thus is separated out of the

Commission's deliberations on acceptable levels of risk. In establishing accept-

able levels of risk, therefore, the Commission has been concerned with injury

and pain to the fetus.

Several ethicists argued cogently before the Commission that the ability

to experience pain is morally relevant to decisions regarding research. Indeed,

the argument was advanced that the ability to experience pain is a more appro-

priate consideration than is viability for purposes of establishing the limits

of intervention into fetal life.

However, scientific opinion is divided on the question of whether the

fetus can experience pain--and on the appropriate indices on which to measure

the experience of pain. Several experts argue that the fetus does not feel pain.

I believe that the Commission has implicitly accepted this view in making

Recommendation (6) regarding research on the fetus during the abortion procedure

and on the nonviable fetus ex utero. Should this view not be correct, and should

the fetus indeed be able to experience pain before the twentieth week of gesta-

tion, I would modify Recommendation (6) in two ways:

First, the Recommendation as it now stands does not specify an acceptable

level of risk. The reason for this omission is essentially as follows: in a

dying subject prior to viability, "diminution of faculties" does not appear to

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be a meaningful index of harm since this index refers largely to future life

expectations. Therefore, the critical meaning of "harm" for such a subject lies

in the possibility of experiencing pain. If the fetus does not feel pain it

cannot be "harmed" in this sense, and thus there is no risk of harm for such a

fetus. It is for this reason that the Commission has not specified an acceptable

level of "risk" for fetuses in this category, although it has been careful to

protect the dignity of the fetus.

Clearly, however, if the fetus does indeed feel pain, then it can be

"harmed" by the above definition of harm. If so, then I would argue that an

acceptable level of risk should be established at the same level as that consid-

ered acceptable for fetuses in utero --namely, "no risk" or "minimal risk."

Second, the Commission has concluded that out of respect for the dying

subject, no interventions are permissible which would alter the duration of life

of the subject--i.e., by shortening or lengthening the dying process (item 6h).

I find the prohibition against shortening the life of the dying fetus to be

acceptable provided the fetus does not feel pain. If the fetus does feel pain,

however, then its dying may be painful and respect for the dying subject may

require that its pain be minimized even if its life-span is shortened in so

doing.

2. The Commission has stated that its provisions regarding therapeutic

and nontherapeutic research directed toward the pregnant woman are not intended

to limit research on improving abortion techniques. I support this stand and

wish to clarify the reasons for my support.

In supporting this statement, I neither condone nor encourage widespread

abortion. However, I do believe that some abortions are both legally and morally

justifiable. It is therefore consonant with the principle of minimizing harm

to develop techniques of abortion that are least harmful. Indeed, under the

present climate of legal freedom to abort and widespread practice of abortion,

adherence to the principle of not-harming may impose an obligation on us to

research abortion technology in order to minimize harm. This obligation arises

not only out of consideration of the health and well-being of the woman but also

from a concern for possible pain or discomfort of the fetus during the abortion

procedure.

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3. Evidence presented to the Commission indicates that there is a strong

emphasis in the law on avoiding possible injury to a child to be born. This

evidence, coupled with the uncertainty of risks in a new class of human subjects,

suggests that considerable importance ought to be attached to the question of

compensation for in jury incurred during research.

The Commission will study this question in depth at a later time, and

therefore has not made any recommendations on compensation at this time. As a

matter of personal opinion, I would like to note that I am reluctant to allow

any research on the living human fetus unless provision has been made for ade-

quate compensation of subjects in jured during research.

4. The Commission's Recommendation on research during the abortion pro-

cedure and on the nonviable fetus ex utero prevents prolongation of the dying

process for purposes of research. This prohibition may appear to have the effect

of preventing research on the development of an artificial placenta.

It is my understanding that such an effect does not necessarily follow.

Steps toward the development of an artificial placenta are prohibited only

through nontherapeutic research; innovative therapy or therapeutic research on

opment of an artificial placenta may proceed, but under more restricted circum-

the possibly viable infant is not only condoned but encouraged. Thus the devel-

stances in which it is limited to therapeutic research or to nontherapeutic

research which does not alter the duration of life. I do not believe that it

was the intention of the Commission to curtail all research toward the develop-

ment of an artificial placenta, nor do I believe that such will be the effect

of the Commission's Recommendations.

Were the Recommendations to have such an effect, however, I would dissent.

Indeed, I would argue that a prematurely delivered fetus that is unable to sur-

vive, given the support of available medical technology, would have an interest

in the development of an artificial placenta that would allow others like it to

survive. Thus it would not be contrary to the interests of that fetus for it

to be subjected to nontherapeutic research in the development of an artificial

placenta.

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In making such an argument, I invoke a principle that I call the "prin-

ciple of proximity": namely, that research is ethically more acceptable the

more closely it approximates what the considered interests of the subject would

reasonably be. For example, Hans Jonas has argued that dying subjects should

not be used in nontherapeutic research, even when they have consented, unless

the research deals directly with the cause from which they are dying; that is,

it is presumed that a dying subject has an interest in his/her own disease which

legitimates research on that disease where research in general would not be

legitimate.

Such a principle is, of course, open to wide interpretation. But I think

it not unreasonable to suggest that the dying fetus would have an interest in

the cause of its dying or in the development of technology which would allow

others like it to survive. On such a principle, one might argue that it is more

ethically acceptable to use dying fetuses with Tay-Sachs disease as subjects in

nontherapeutic research on Tay-Sachs disease than in nontherapeutic research on

general fetal pharmacology. Similarly, one might argue that it is ethically

acceptable to use nonviable fetuses ex utero as subjects in nontherapeutic

research on the development of an artificial placenta. The development of a

full rationale for such a position would require an analysis along the lines

suggested by McCormick and Toulmin, and I cannot attempt that here. At this

point I simply wish to suggest that I believe it is possible to argue for both

therapeutic and nontherapeutic research directed toward the development of an

artificial placenta.

5. Finally, members of the Commission disagreed about changes in the

timing or method of abortion in relation to research. Recommendation (10) States

clearly that the recommendations of a physician regarding timing and method of

abortion should not be determined by the design or conduct of nontherapeutic

research. I am in full agreement with this Recommendation.

The provision in Recommendation (6) (item g), however, is more ambiguous.

I would argue that changes in timing or method of abortion are ethically accept-

able provided that they are freely chosen by the woman and that she has been fully

informed of all possible risks from such changes. I base this argument on the

right of any patient to be informed about alternative courses of treatment and

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to choose between them. It seems to me that the pregnant woman, as a patient,

may choose the timing and method of abortion, provided that she has been fully

informed of the following: 1) the relation of alternative methods of abortion

to possible research on the fetus; 2) risks to herself and to possible future

children of alternative possible methods of abortion; and 3) procedures which

would be introduced into the abortion as part of the research design which would

not be medically indicated.

Some members of the Commission have argued that a woman might choose such

changes provided that they entail no additional risk. While I appreciate the

concern to protect the woman's health and well-being, such a restriction seems

to me a violation of her right to freedom of choice as a patient. Thus I would

allow a woman to choose to delay her abortion until the second trimester for

purposes of research, provided that she has been fully informed of all risks in

so doing. One restriction seems imperative to me, however: in no case, should

she be allowed to delay the abortion beyond the twentieth week of gestation for

research purposes. This position is reflected in the Deliberations and Conclu-

sions of the Commission's Report.

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